Glucemia, almidón y azúcar en su contexto
Glucemia, almidón y azúcar en su contexto
Monosacárido: azúcar simple; ejemplos: glucosa, fructosa, ribosa, galactosa (la galactosa también se denomina cerebrosa, azúcar cerebral).
Disacárido: dos monosacáridos unidos; ejemplos: sacarosa, lactosa, maltosa.
Oligosacárido: cadena corta de monosacáridos, incluidos los disacáridos y las cadenas ligeramente más largas.
Polisacárido — ejemplo, almidón, celulosa, glucógeno.
Glicación: unión de un azúcar a una proteína.
Lipólisis — liberación de ácidos grasos libres a partir de los triglicéridos, la forma neutra en la que se almacenan las grasas, unidas a la glicerina.
En la década de 1920, se pensaba que la "diabetes" era una enfermedad por déficit de insulina. Con el tiempo, las mediciones de insulina demostraron que los "diabéticos" solían tener cantidades normales de insulina, o superiores a las normales. En la actualidad existen "dos tipos de diabetes" y se cree que la enfermedad pronto se subdividirá aún más.
Las enfermedades degenerativas asociadas a la hiperglucemia y comúnmente denominadas diabetes, sólo están indirectamente relacionadas con la insulina, y como enfoque para comprender o tratar la diabetes, el "índice glucémico" de los alimentos es inútil. Fisiológicamente, no tiene ninguna utilidad constructiva, y muy poco significado.
La insulina es importante en la regulación del azúcar en sangre, pero su importancia se ha exagerado debido a la industria de la diabetes/insulina. Se ha descubierto que la insulina en sí sólo representa alrededor del 8% de la "actividad similar a la insulina" de la sangre, siendo probablemente el potasio el factor más importante. Probablemente no hay ningún proceso en el cuerpo que no afecte potencialmente al azúcar en sangre.
El glucagón, el cortisol, la adrenalina, la hormona del crecimiento y la tiroides tienden a aumentar la glucemia, pero es frecuente interpretar la hiperglucemia como "diabetes", sin medir ninguno de estos factores. Incluso cuando se diagnostica "diabetes insulinodependiente", no se acostumbra a medir la insulina para ver si realmente es deficiente, antes de recetar insulina. La gente se resigna a toda una vida de inyecciones de insulina, sin saber por qué su nivel de azúcar en sangre es alto.
La liberación de insulina también se ve estimulada por aminoácidos como la leucina, y la insulina estimula a las células para que absorban aminoácidos y sinteticen proteínas. Dado que la insulina reduce el azúcar en sangre a medida que elimina los aminoácidos, ingerir una gran cantidad de proteínas sin hidratos de carbono puede provocar un descenso brusco del azúcar en sangre. Esto provoca la liberación de adrenalina y cortisol, que elevan el azúcar en sangre.
La adrenalina hace que los ácidos grasos pasen a la sangre desde las reservas de grasa, especialmente si las reservas de glucógeno del hígado están agotadas, y el cortisol hace que las proteínas de los tejidos se descompongan en aminoácidos, algunos de los cuales se utilizan en lugar de los hidratos de carbono. Los ácidos grasos insaturados, la adrenalina y el cortisol provocan resistencia a la insulina.
"La opinión profesional" puede propagarse unas 10.000 veces más rápido de lo que la investigación puede evaluarla o, como dijo C. H. Spurgeon: "Una mentira da la vuelta al mundo mientras la Verdad se pone las botas".
En la década de 1970, los dietistas empezaron a hablar del valor de incluir "carbohidratos complejos" en la dieta. Muchos dietistas (todos menos uno de los dietistas registrados que yo conocía) afirmaban que los almidones se absorbían más lentamente que los azúcares, por lo que deberían alterar menos los niveles de azúcar e insulina en sangre. Se recomendaba comer cereales integrales y legumbres, y evitar los zumos de fruta.
Estas recomendaciones, y la ideología que las sustenta, siguen campando a sus anchas en la cultura de Estados Unidos, fomentadas por el Departamento de Agricultura, la Asociación Dietética Americana, la Asociación Americana de Diabetes e innumerables departamentos universitarios de economía doméstica, dietética o nutrición.
A juzgar por las declaraciones presentes y pasadas de la Asociación Dietética Americana, creo que algún tipo de defecto cerebral institucional podría explicar sus recomendaciones. Aunque la asociación dietética reconoce ahora débilmente que los azúcares no elevan el azúcar en sangre más rápidamente que los almidones, no pueden alejarse de sus antiguas y absurdas recomendaciones, que nunca estuvieron justificadas científicamente: "Coma más almidones, como pan, cereales y verduras feculentas: 6 raciones al día o más. Empiece el día con cereales fríos (secos) con leche descremada o desnatada o un panecillo con una cucharadita de mermelada. Ponga el almidón en el centro: pasta con salsa de tomate, patata asada con chile, arroz y carne y verduras salteadas. Añade judías negras, maíz o garbanzos cocidos a las ensaladas o guisos".
La asociación de la Asociación Dietética con General Mills, el imperio de los cereales para el desayuno, (y con Kellog, Nabisco y muchos otros gigantes de la industria alimentaria) podría tener algo que ver con sus opiniones sobre el almidón. Las embolias de los granos de almidón pueden causar daños cerebrales, pero el dinero también puede hacer que la gente diga estupideces.
En un antiguo experimento, una rata fue alimentada por sonda con diez gramos de pasta de almidón de maíz, y luego anestesiada. Diez minutos después de la alimentación masiva por sonda, el profesor pidió a los estudiantes que averiguaran hasta dónde se había desplazado el almidón por el canal alimentario. No se encontró ni rastro de la pasta blanca, lo que demuestra la rapidez con la que el almidón puede ser digerido y absorbido. El rapidísimo aumento del azúcar en sangre estimula la liberación masiva de insulina y convierte rápidamente gran parte de los hidratos de carbono en grasa.
Fue este tipo de experimento el que dio lugar al concepto de "índice glucémico", que clasifica los alimentos según su capacidad para elevar el azúcar en sangre. David Jenkins, en 1981, sabía lo suficiente sobre los antiguos estudios de la digestión del almidón como para darse cuenta de que los dietistas habían creado un culto peligroso en torno a los "carbohidratos complejos", e hizo una serie de mediciones que demostraron que el almidón es más "glucémico" que la sacarosa.
Pero se limitó a utilizar para la comparación la cantidad de aumento de glucosa en sangre durante las dos primeras horas tras la ingestión de la muestra de alimento, comparada con la que se produce tras la ingestión de glucosa pura, olvidando los hechos fisiológicamente complejos, todos los procesos que intervienen para que una determinada cantidad de glucosa esté presente en la sangre durante un determinado tiempo. (Incluso el sabor dulce, sin tragar nada, puede estimular la liberación de glucagón, que eleva la glucemia).
Más importante que la vacuidad fisiológica de una simple medición glucémica era la ideología en la que se desarrollaba toda la cuestión, a saber, la idea de que la diabetes (concebida como hiperglucemia crónica) está causada por comer demasiado azúcar, es decir, la hiperglucemia crónica la enfermedad está causada por la hiperglucemia recurrente de la gula azucarera.
Los experimentos de Bernardo Houssay (premio Nobel de 1947) en los años 40, en los que el azúcar y el aceite de coco protegían contra la diabetes, seguidos de la demostración de Randle del antagonismo entre las grasas y la asimilación de la glucosa, y el creciente reconocimiento de que los ácidos grasos poliinsaturados provocan resistencia a la insulina y dañan el páncreas, han dejado claro que la obsesión dietética por el azúcar en relación con la diabetes ha sido una peligrosa distracción que ha retrasado la comprensión de las enfermedades metabólicas degenerativas.
Empezando por la industria de la insulina, la cultura de la diabetes y el azúcar se ha ido mitificando, expandiendo y modificando a medida que nuevas industrias comerciales encontraban formas de sacar provecho de ella. Los aceites de semillas, los aceites de pescado, los cereales para el desayuno, los productos de soja y otras cosas que nunca comió ningún animal en millones de años de evolución se han convertido en habituales como "alimentos", incluso como "alimentos saludables".
Aunque muchas cosas condicionan la velocidad a la que aumenta el azúcar en sangre después de comer hidratos de carbono y afectan a la forma en que se metaboliza la glucosa en sangre, lo que hace que la idea de un "índice glucémico" sea muy engañosa, es cierto que las respuestas del azúcar en sangre y la insulina a los distintos alimentos tienen algunos efectos significativos sobre la fisiología y la salud.
El almidón y la glucosa estimulan eficazmente la secreción de insulina, y eso acelera la disposición de la glucosa, activando su conversión en glucógeno y grasa, así como su oxidación. La fructosa inhibe la estimulación de la insulina por la glucosa, lo que significa que comer azúcar común, sacarosa (un disacárido, compuesto de glucosa y fructosa), en lugar de almidón, reducirá la tendencia a almacenar grasa. Comer "carbohidratos complejos", en lugar de azúcares, es una forma razonable de promover la obesidad.
Comer almidón, al aumentar la insulina y bajar el azúcar en sangre, estimula el apetito, haciendo que la persona coma más, por lo que el efecto sobre la producción de grasa es mucho mayor que cuando se comen cantidades iguales de azúcar y almidón. La propia obesidad se convierte entonces en un factor fisiológico adicional; las células grasas crean algo análogo a un estado inflamatorio. No hay nada malo en una dieta rica en hidratos de carbono, e incluso una dieta rica en almidón no es necesariamente incompatible con una buena salud, pero cuando se dispone de alimentos mejores deberían utilizarse en lugar de los almidones. Por ejemplo, las frutas tienen muchas ventajas sobre los cereales, además de la diferencia entre azúcar y almidón. El consumo de pan y pasta está fuertemente asociado a la aparición de diabetes, el consumo de fruta tiene una fuerte asociación inversa.
Aunque la fructosa y la sacarosa puras producen menos glucemia que la glucosa y el almidón, los diferentes efectos de las frutas y los cereales sobre la salud no pueden reducirse a sus efectos sobre la glucemia.
El zumo de naranja y la sacarosa tienen un índice glucémico más bajo que el almidón o el pan integral o blanco, pero es habitual que los dietistas argumenten en contra del consumo de zumo de naranja, porque su índice es el mismo que el de la Coca Cola.
Pero, si el índice glucémico es muy importante, para ser racionales tendrían que argumentar que la Coca Cola o el zumo de naranja deberían sustituir al pan blanco.
Tras décadas de "educación" para promover el consumo de alimentos ricos en almidón, la obesidad es un problema mayor que nunca, y mueren más personas de diabetes que antes. La incidencia específica por edad de la mayoría de los cánceres también está aumentando, y hay pruebas de que el almidón, como la pasta, contribuye al cáncer de mama, y posiblemente a otros tipos de cáncer.
La epidemiología parece sugerir que los carbohidratos complejos causan diabetes, enfermedades cardiacas y cáncer. Si el índice glucémico se considera desde el punto de vista de la teoría de que la hiperglucemia, por medio de la "glucotoxicidad", provoca la destrucción de las proteínas por glicación, lo que se observa en la diabetes y la vejez, podría parecer sencillo y obvio.
[NB: Para ver la tabla en condiciones, usad un ordenador o dirigíos al articulo oficial.]
Fructosa
Lactosa
Miel
Jarabe de maíz rico en fructosa
Sacarosa
Glucosa
Pastillas de glucosa
Maltodextrina
Maltosa
Zumo de piña
Melocotón en conserva
Zumo de pomelo
Zumo de naranja
Pan de harina de cebada
Pan de trigo, alto contenido en fibra
Pan de trigo, harina integral
Pan tostado melba
Pan de trigo blanco
Bagel blanco
Panecillos Kaise
Pan de molde integral
Pan relleno
Pan de trigo Wonderwhite
Pan de trigo sin gluten
Baguette
Tortillas para tacos
Harina de maíz
Mijo
Arroz, Pelde
Arroz, Sunbrown Quick
Tapioca hervida con leche
Arroz, caldoso
Arroz vaporizado bajo en amilosa
Arroz, blanco, bajo en amilosa
Arroz, instantáneo, hervido 6 min
LISTA GLICEMICA
32
65
83
89
92
137
146
150
150
66
67
69
74
95
97
99
100
101
103
104
105
106
112
129
136
97
98
101
109
114
115
124
124
126
128
Pan blanco
22
46
58
62
64
96
102
105
105
46
47
48
52
67
68
69
70
71
72
73
74
74
78
90
95
68
69
71
76
80
81
87
87
88
90
Basado en gluc.
Pero hay muchas razones para cuestionar esa teoría.
La oxidación del azúcar es eficiente desde el punto de vista metabólico en muchos aspectos, incluido el ahorro de consumo de oxígeno. Produce más dióxido de carbono que la oxidación de las grasas, y el dióxido de carbono tiene muchas funciones protectoras, como aumentar la actividad del ciclo de Krebs e inhibir el daño tóxico a las proteínas. La glicación de las proteínas se produce bajo estrés, cuando se produce menos dióxido de carbono, y las proteínas están normalmente protegidas por el dióxido de carbono.
Cuando el azúcar (o el almidón) se convierte en grasa, las grasas serán saturadas, o en la serie derivada de los ácidos grasos monoinsaturados omega -9. Cuando no se dispone de azúcar en la dieta, el glucógeno almacenado proporcionará algo de glucosa (normalmente durante unas horas, hasta un día), pero a medida que se agote, las proteínas se metabolizarán para proporcionar azúcar.
Si se ingieren proteínas sin hidratos de carbono, se estimulará la secreción de insulina, lo que reducirá el azúcar en sangre y activará la respuesta al estrés, provocando la secreción de adrenalina, cortisol, hormona del crecimiento, prolactina y otras hormonas. La adrenalina movilizará el glucógeno del hígado y (junto con otras hormonas) movilizará los ácidos grasos, principalmente de las células grasas. El cortisol activará la conversión de proteínas en aminoácidos, y después en grasa y azúcar, para su uso como energía. (Si la dieta no contiene suficientes proteínas para mantener los órganos esenciales, especialmente el corazón, los pulmones y el cerebro, éstos se abastecen de proteínas procedentes de los músculos esqueléticos.
Debido a la composición en aminoácidos de las proteínas musculares, su destrucción estimula la formación de cortisol adicional, para acelerar el movimiento de aminoácidos de los tejidos menos importantes a los esenciales).
La condición diabética es similar en muchos aspectos al estrés, la inflamación y el envejecimiento, por ejemplo en la elevación crónica de los ácidos grasos libres, y en varios mediadores de la inflamación, como el factor de necrosis tumoral (TNF).
Más que la hiperglucemia sostenida que se mide para determinar el índice glucémico, creo que la acción "diabetógena" o "cancerígena" del almidón tiene que ver con la reacción de estrés que sigue a la intensa estimulación de la liberación de insulina. Esto se observa más fácilmente después de ingerir una gran cantidad de proteínas. La insulina se segrega en respuesta a los aminoácidos, y además de estimular a las células para que cojan los aminoácidos y los conviertan en proteínas, la insulina también disminuye el azúcar en sangre.
Esta disminución del azúcar en sangre estimula la formación de muchas hormonas, entre ellas el cortisol, y bajo la influencia del cortisol se producen tanto azúcar como grasa por la descomposición de las proteínas, incluidas las que ya forman los tejidos del cuerpo. Al mismo tiempo, la adrenalina y otras hormonas provocan la aparición de ácidos grasos libres en la sangre.
Desde los trabajos de Cushing y Houssay, se ha comprendido que el azúcar en la sangre está controlado por hormonas antagónicas: Si se elimina la hipófisis junto con el páncreas, la falta de insulina no provoca hiperglucemia. Si algo aumenta un poco el cortisol, el cuerpo puede mantener una glucemia normal segregando más insulina, pero eso tiende a aumentar la producción de cortisol. Un cierto grado de glucemia se produce por un equilibrio particular entre hormonas opuestas.
El triptófano, procedente de las proteínas alimentarias o del catabolismo muscular, se convierte en serotonina que activa las hormonas del estrés hipofisarias, aumentando el cortisol, e intensificando el catabolismo, que libera más triptófano. Suprime la función tiroidea, lo que conduce a una mayor necesidad de las hormonas del estrés. La serotonina perjudica la oxidación de la glucosa y contribuye a muchos de los problemas asociados a la diabetes.
"Diabetes" es a menudo el diagnóstico, cuando el exceso de cortisol es el problema. Tradicionalmente no se han medido las hormonas antes de diagnosticar la diabetes y recetar insulina u otra sustancia química para bajar el azúcar en sangre. Algunos de los peores efectos de la "diabetes", incluido el daño retiniano, son causados o exacerbados por la propia insulina.
Los fármacos antiserotonina a veces pueden aliviar el estrés y normalizar el azúcar en sangre. Recientemente se ha descubierto que el simple hecho de comer sacarosa frena el sistema hormonal del estrés ("A new perspective on glucocorticoid feedback: relation to stress, carbohydrate feeding and feeling better", J Neuroendocrinol 13(9), 2001, KD Laugero).
Los ácidos grasos libres liberados por las hormonas del estrés sirven como combustible suplementario y aumentan el consumo de oxígeno y la producción de calor (este aumento de la demanda de oxígeno es un problema para el corazón cuando se ve obligado a oxidar los ácidos grasos. ) Pero si las grasas almacenadas resultan ser poliinsaturadas, dañan los vasos sanguíneos y las mitocondrias, suprimen la función tiroidea y provocan la "glicación" de las proteínas. También dañan el páncreas y alteran la secreción de insulina.
Un pequeño estrés repetido, o una sobreestimulación de la secreción de insulina, tiende gradualmente a amplificarse por los efectos del triptófano y de los ácidos grasos poliinsaturados, ya que estas grasas aumentan la formación de serotonina, y la serotonina aumenta la liberación de las grasas.
El nombre, "glicación", indica la adición de grupos de azúcar a las proteínas, como ocurre en la diabetes y la vejez, pero cuando se probó en un experimento controlado, la peroxidación lipídica de los ácidos grasos poliinsaturados produce el daño proteico unas 23 veces más rápido que los azúcares simples (Fu, et al., 1996).Y la oxidación de las grasas en lugar de la glucosa significa que las proteínas no tendrán tanto dióxido de carbono protector combinado con sus átomos de nitrógeno reactivos, por lo que es probable que la diferencia real en el organismo sea mayor que la observada por Fu, et al.
Estos productos de la peroxidación lipídica, HNE, MDA, acroleína, glioxal y otros aldehídos altamente reactivos, dañan las mitocondrias, reduciendo la capacidad de oxidar el azúcar y de producir energía y dióxido de carbono protector. El aceite de pescado, que es extremadamente inestable en presencia de oxígeno y metales como el hierro, produce muy rápidamente algunos de estos productos peligrosos. Los "ácidos grasos esenciales" poliinsaturados y sus productos, el ácido araquidónico y muchos de los materiales similares a las prostaglandinas, también los producen.
Cuando la glucosa no puede ser oxidada, por cualquier razón, se produce una reacción de estrés, que moviliza ácidos grasos libres. Los fármacos que se oponen a las hormonas (como la adrenalina o la hormona del crecimiento) que liberan ácidos grasos libres se han utilizado para tratar la diabetes, porque la disminución de los ácidos grasos libres puede restablecer la oxidación de la glucosa.
Las exposiciones breves a los ácidos grasos poliinsaturados pueden dañar las células secretoras de insulina del páncreas y las mitocondrias en las que tiene lugar la producción de energía oxidativa. La exposición prolongada provoca daños progresivos. De forma aguda, los ácidos grasos poliinsaturados libres provocan un aumento de la permeabilidad capilar, lo que puede detectarse al principio de la "resistencia a la insulina" o "diabetes". Tras una exposición crónica, la permeabilidad aumenta y aparece albúmina en la orina, ya que las proteínas se escapan de los vasos sanguíneos. La retina, el cerebro y otros órganos resultan dañados por las fugas de los capilares.
Los vasos sanguíneos y otros tejidos también resultan dañados por el aumento crónico de cortisol y, al menos en algunos tejidos (el sistema inmunitario es el más sensible a la interacción), las grasas poliinsaturadas aumentan la capacidad del cortisol para matar las células.
Cuando las células están estresadas, es probable que desperdicien glucosa de dos maneras, convirtiendo parte de ella en ácido láctico, y convirtiendo parte en ácidos grasos, incluso mientras se oxidan las grasas, en lugar del azúcar que está disponible.
La hormona del crecimiento y la adrenalina, las hormonas inducidas por el estrés, estimulan la oxidación de los ácidos grasos, así como su liberación del almacenamiento, por lo que la corrección del metabolismo energético requiere la minimización de las hormonas del estrés, y de los ácidos grasos libres. La prolactina, la ACTH y los estrógenos también provocan el desplazamiento del metabolismo hacia los ácidos grasos. El azúcar y la hormona tiroidea (T3, triyodotironina) corrigen muchas partes del problema. La conversión de T4 en T3 activa requiere glucosa, y en la diabetes, las células están privadas de glucosa.
Lógicamente, todos los diabéticos serían funcionalmente hipotiroideos. Proporcionar T3 y azúcar tiende a desplazar el metabolismo energético de la oxidación de las grasas a la oxidación del azúcar. La niacinamida, utilizada en dosis moderadas, puede ayudar de forma segura a frenar la producción excesiva de ácidos grasos libres, y también ayuda a limitar la conversión derrochadora de glucosa en grasa. Existen pruebas de que los diabéticos sufren una deficiencia crónica de niacina. El exceso de ácidos grasos en la sangre probablemente desvía el triptófano de la síntesis de niacina a la síntesis de serotonina.
El sodio, que se pierde en el hipotiroidismo y la diabetes, aumenta la energía celular. Los diuréticos, que provocan la pérdida de sodio, pueden causar una diabetes aparente, con aumento de glucosa y grasas en la sangre. La tiroides, el sodio y la glucosa trabajan en estrecha colaboración para mantener la energía y la estabilidad celular.
Las grasas saturadas del aceite de coco son similares a las que sintetizamos nosotros mismos a partir del azúcar. Las grasas saturadas, y las grasas poliinsaturadas sintetizadas por las plantas, tienen efectos muy diferentes en muchos procesos fisiológicos importantes. En todos los casos que conozco, las grasas poliinsaturadas vegetales tienen efectos perjudiciales para nuestra fisiología.
Por ejemplo, se unen a las proteínas "receptoras" del cortisol, la progesterona y el estrógeno, y a todas las proteínas importantes relacionadas con la función tiroidea, así como a las vesículas que recogen sustancias transmisoras nerviosas, como el ácido glutámico. Permiten que el ácido glutámico lesione y mate las células a través de una estimulación excesiva; este proceso es similar al daño nervioso causado por el veneno de cobra, y otras toxinas.
El exceso de cortisol hace que las células nerviosas sean más sensibles a la excitotoxicidad, pero las células se protegen si se les suministra una cantidad inusualmente grande de glucosa.
Las células del timo son muy sensibles a los daños provocados por el estrés o el cortisol, pero también pueden ser rescatadas si se les suministra una cantidad extra de glucosa suficiente para compensar el cortisol.
Los ácidos grasos poliinsaturados tienen el efecto contrario, sensibilizando las células del timo al cortisol. Esto explica en parte los efectos inmunosupresores de las grasas poliinsaturadas. (Los pacientes con SIDA tienen un aumento de cortisol y ácidos grasos poliinsaturados en sangre [E.A. Núñez, 1988]).
Los ácidos grasos insaturados activan las hormonas del estrés, el azúcar las frena. Simplemente haciendo a los animales "deficientes" en los aceites vegetales insaturados (lo que les permite sintetizar su propia serie de grasas poliinsaturadas animales, que son muy estables), les protege contra la diabetes "autoinmune", y contra una variedad de otros desafíos "inmunológicos". La carencia de "ácidos grasos esenciales" aumenta la oxidación de la glucosa, ya que aumenta la tasa metabólica en general. Las grasas saturadas mejoran la respuesta secretora de insulina a la glucosa.
Los efectos protectores del azúcar, y los efectos nocivos de un metabolismo excesivo de las grasas, son ahora ampliamente reconocidos, en todos los campos de la fisiología. Las grasas vegetales insaturadas, el ácido linoleico y linolénico y sus derivados, como el ácido araquidónico y los aceites de pescado de cadena larga, tienen efectos excitatorios, promotores del estrés, que desvían el metabolismo de la oxidación de la glucosa y, finalmente, destruyen por completo el metabolismo respiratorio. Dado que la lesión y la muerte celular implican generalmente un desequilibrio entre la excitación y la capacidad de producir energía, es significativo que la oxidación de los ácidos grasos insaturados parezca consumir energía, disminuyendo el ATP celular (Clejan, et al, 1986).
La mayor parte del daño tisular relacionado con la edad clasificado como "productos finales de la glicación" (o "productos finales de la glicación avanzada", AGE) se produce por la descomposición de las grasas poliinsaturadas, más que por los azúcares, y esto se minimizaría mediante la oxidación protectora de la glucosa a dióxido de carbono. Las proteínas del tipo adecuado, en la cantidad adecuada, son esenciales para reducir el estrés. La gelatina, con su equilibrio de aminoácidos antiinflamatorios, ayuda a regular el metabolismo de las grasas.
Las acciones antiinflamatorias de la aspirina son generalmente importantes cuando las grasas poliinsaturadas están produciendo cambios inflamatorios y degenerativos, y la aspirina previene muchos de los problemas asociados con la diabetes, reduciendo la filtración vascular. Mejora la respiración mitocondrial (De Cristobal, et al., 2002) y ayuda a regular el azúcar y los lípidos en sangre (Yuan, et al., 2001). La amplia gama de efectos beneficiosos de la aspirina es probablemente análoga a la de la vitamina E, siendo proporcional a la protección contra la amplia gama de efectos tóxicos de los ácidos grasos "esenciales" poliinsaturados.
Texto original traducido por SoliferroDiabetes Care 1993 Sep;16(9):1301-5. Metabolic effects of dietary sucrose in type II diabetic subjects. Bantle JP, Swanson JE, Thomas W, Laine DC “CONCLUSIONS--A high sucrose diet did not adversely affect glycemia or lipemia in type II diabetic subjects.”
Am J Physiol 1997 Nov;273(5 Pt 1):C1732-8. Glycolysis inhibition by palmitate in renal cells cultured in a two-chamber system. Bolon C, Gauthier C, Simonnet H “…palmitate promoted a long-term decrease in lactate production and sustained excellent cellular growth. After 4 days of contact, decreased glycolysis was maintained even in the absence of carnitine….”
Diabetes 1989 Oct;38(10):1314-9. Effects of fish oil supplementation on glucose and lipid metabolism in NIDDM. Borkman M, Chisholm DJ, Furler SM, Storlien LH, Kraegen EW, Simons LA, Chesterman CN. Garvan “In summary, dietary fish oil supplementation adversely affected glycemic control in NIDDM subjects without producing significant beneficial effects on plasma lipids. The effect of safflower oil supplementation was not significantly different from fish oil, suggesting that the negative effects on glucose metabolism may be related to the extra energy or fat intake.” Randomized Controlled Trial
Ann Clin Lab Sci 1988 Jul-Aug;18(4):337-43. Effects of peroxidized polyunsaturated fatty acids on mitochondrial function and structure: pathogenetic implications for Reye's syndrome. Brown RE, Bhuvaneswaran C, Brewster M. “Linoleic acid, a polyunsaturated fatty acid, is a constituent of margosa oil which has been implicated as a cause of Reye's syndrome (RS) in infants. Increased concentrations of polyunsaturated fatty acids have been found in sera from patients with RS.” Isolated rat liver mitochondria exposed to the peroxidized (but not unperoxidized) methyl esters of linoleic (C18:2) or linolenic (C18:3) acids showed decreases in state 3 and uncoupled respiratory rates and in respiratory control and ADP/O ratios. In addition, they caused mitochondrial swelling as demonstrated spectrophotometrically. Between the two, the peroxidized methyl ester of linolenic acid was more toxic and was capable of inducing high amplitude swelling ultrastructurally similar to that seen in the hepatocytes of RS victims. The ability of rat liver mitochondria to oxidize glutamate was inversely related to the peroxide concentration in the medium.”
J Neurochem 1982 Feb;38(2):525-31. Phospholipid degradation and cellular edema induced by free radicals in brain cortical slices. Chan PH, Yurko M, Fishman RA. “These data suggest that lipases are activated by free radicals and lipid peroxides in the pathogenesis of cellular swelling.”
J Neurochem 1988 Apr;50(4):1185-93. Induction of intracellular superoxide radical formation by arachidonic acid and by polyunsaturated fatty acids in primary astrocytic cultures. Chan PH, Chen SF, Yu AC. “Other PUFAs, including linoleic acid, linolenic acid, and docosahexaenoic acid, were also effective in stimulating NBF formation in astrocytes, whereas saturated palmitic acid and monounsaturated oleic acid were ineffective. Similar effects of these PUFAs were observed in malondialdehyde formation in cells and lactic acid accumulation in incubation medium. These data indicate that both membrane integrity and cellular metabolism were perturbed by arachidonic acid and by other PUFAs.”
Can J Biochem 1978 Feb;56(2):111-6. Uncoupling activity of endogenous free fatty acids in rat liver mitochondria. Chan SH, Higgins E Jr.
J Neurochem 1980 Oct;35(4):1004-7. Transient formation of superoxide radicals in polyunsaturated fatty acid-induced brain swelling. Chan PH, Fishman RA. “The polyunsaturated fatty acids linoleic acid (18:2), linolenic acid (18:3), arachidonic acid (20:4), and docosahexaenoic acid (22:6) caused brain swelling concomitant with increases in superoxide and membrane lipid peroxidation. Palmitic acid (16:0) and oleic acid (18:1) had no such effect.” “These in vitro data support the hypothesis that both superoxide radicals and lipid peroxidation are involved in the mechanism of polyunsaturated fatty acid-induced brain edema.”
Arch Biochem Biophys 1986 May 1;246(2):820-8. Effect of growth hormone on fatty acid oxidation: growth hormone increases the activity of 2,4-dienoyl-CoA reductase in mitochondria. Clejan S, Schulz H. “Rates of respiration supported by polyunsaturated fatty acylcarnitines, in contrast to rates observed with palmitoylcarnitine or oleoylcarnitine, were slightly lower in hypophysectomized rats than in normal rats, but were higher in hypophysectomized rats treated with growth hormone. The effects were most pronounced with docosahexaenoylcarnitine, the substrate with the highest degree of unsaturation. Since uncoupling of mitochondria with 2,4-dinitrophenol resulted in lower rates of docosahexaenoylcarnitine-supported respiration, while substitution of ATP for ADP yielded higher rates, it appears that energy is required for the effective oxidation of polyunsaturated fatty acids. Growth hormone treatment of hypophysectomized rats caused a threefold increase in t`he activity of 2,4-dienoyl-CoA reductase or 4-enoyl-CoA reductase (EC 1.3.1.34) in mitochondria, but not in peroxisomes.” “Rates of acetoacetate formation from linolenoylcarnitine, but not from palmitoylcarnitine, were stimulated by glutamate in mitochondria from hypophysectomized rats and hypophysectomized rats treated with growth hormone. All data together lead to the conclusion that the mitochondrial oxidation of highly polyunsaturated fatty acids is limited by the availability of NADPH and the activity of 2,4-dienoyl-CoA reductase which is induced by growth hormone treatment.”
V. Coiro, et al., "Low-dose ovine corticotropin-releasing hormone stimulation test in diabetes mellitus with or without neuropathy," Metabolism--Clinical and Experimental 44(4), 538-542, 1995. "...basal and CRH-induced cortisol levels were significantly higher in diabetics than in normal controls." "...even uncomplicated diabetes mellitus is associated with adrenal hyperfunction."
Stroke 2002 Jan;33(1):261-7. Inhibition of glutamate release via recovery of ATP levels accounts for a neuroprotective effect of aspirin in rat cortical neurons exposed to oxygen-glucose deprivation. De Cristobal J, Cardenas A, Lizasoain I, Leza JC, Fernandez-Tome P, Lorenzo P, Moro MA. “Aspirin is preventive against stroke not only because of its antithrombotic properties but also by other direct effects.” “Aspirin inhibited OGD-induced neuronal damage at concentrations lower (0.3 mmol/L) than those reported to act via inhibition of the transcription factor nuclear factor-kappaB (which are >1 mmol/L), an effect that correlated with the inhibition caused by aspirin on glutamate release. This effect was shared by sodium salicylate but not by indomethacin, thus excluding the involvement of cyclooxygenase. A pharmacological dissection of the components involved indicated that aspirin selectively inhibits the increase in extracellular glutamate concentration that results from reversal of the glutamate transporter, a component of release that is due to ATP depletion. Moreover, aspirin-afforded neuroprotection occurred in parallel with a lesser decrease in ATP levels after OGD. Aspirin elevated ATP levels not only in intact cortical neurons but also in isolated brain mitochondria, an effect concomitant with an increase in NADH-dependent respiration by brain submitochondrial particles.” “Taken together, our present findings show a novel mechanism for the neuroprotective effects of aspirin, which takes place at concentrations in the antithrombotic-analgesic range, useful in the management of patients with high risk of ischemic events.”
Diabetes 2002 Jun;51(6):1825-33. The composition of dietary fat directly influences glucose-stimulated insulin secretion in rats. Dobbins RL, Szczepaniak LS, Myhill J, Tamura Y, Uchino H, Giacca A, McGarry JD. “Insulin responses during hyperglycemic clamps were augmented by saturated but not unsaturated fat (580 +/- 25, 325 +/- 30, and 380 +/- 50 pmol x l(-1) x min(-1) in Lard, Soy, and Low-Fat groups, respectively).” “These data indicate that prolonged exposure to saturated fat enhances GSIS (but this does not entirely compensate for insulin resistance), whereas unsaturated fat, given in the diet or by infusion, impairs GSIS.”
C. Douillet and M. Ciavatti, "Effect of vitamin E treatment on tissue fatty acids and cholesterol content in experimental diabetes," J. Nutr. Biochem. 6(6), 319-326, 1995. "Diabetes induced a decrease of monounsaturated fatty acids and particularly palmitoleic acid in all studied tissues: liver, aorta, plasma." “C18:3 n-6 and C20:4 n-6 were increased by diabetes.”
Diabetologia 1992 Feb;35(2):165-72. Long-term effects of linoleic-acid-enriched diet on albuminuria and lipid levels in type 1 (insulin-dependent) diabetic patients with elevated urinary albumin excretion. Dullaart RP, Beusekamp BJ, Meijer S, Hoogenberg K, van Doormaal JJ, Sluiter WJ. “We conducted a 2-year prospective randomised study to investigate the effects of a linoleic-acid-enriched diet on albuminuria and lipid levels in Type 1 (insulin-dependent) diabetic patients with elevated urinary albumin excretion (overnight urinary albumin excretion rate between 10 and 200 micrograms/min).” “Clinical characteristics, albuminuria, blood pressure, glomerular filtration rate, metabolic control and dietary composition were similar in the two groups at baseline. In the high linoleic acid diet group, linoleic intake rose from 7 +/- 4 to 11 +/- 2 energy % and polyunsaturated:saturated fatty acids ratio rose from 0.60 +/- 0.28 to 0.96 +/- 0.16 (p less than 0.001 compared to usual diet group). The median increase albuminuria was 58% (95% confidence interval, 13 to 109) during the first year (p less than 0.02) and 55% (95% confidence interval, 11 to 127) (p less than 0.01) during the second year.”
J Biol Chem 1996 Apr 26;271(17):9982-6. The advanced glycation end product, Nepsilon-(carboxymethyl)lysine, is a product of both lipid peroxidation and glycoxidation reactions. Fu MX, Requena JR, Jenkins AJ, Lyons TJ, Baynes JW, Thorpe SR. Nepsilon-(Carboxymethyl)lysine (CML) is an advanced glycation end product formed on protein by combined nonenzymatic glycation and oxidation (glycoxidation) reactions. We now report that CML is also formed during metal-catalyzed oxidation of polyunsaturated fatty acids in the presence of protein. During copper-catalyzed oxidation in vitro, the CML content of low density lipoprotein increased in concert with conjugated dienes but was independent of the presence of the Amadori compound, fructoselysine, on the protein. CML was also formed in a time-dependent manner in RNase incubated under aerobic conditions in phosphate buffer containing arachidonate or linoleate; only trace amounts of CML were formed from oleate. After 6 days of incubation the yield of CML in RNase from arachidonate was approximately 0.7 mmol/mol lysine compared with only 0.03 mmol/mol lysine for protein incubated under the same conditions with glucose. Glyoxal, a known precursor of CML, was also formed during incubation of Rnase with arachidonate. These results suggest that lipid peroxidation, as well as glycoxidation, may be an important source of CML in tissue proteins in vivo and that CML may be a general marker of oxidative stress and long term damage to protein in aging, atherosclerosis, and diabetes.
J Nutr 2000 Oct;130(10):2503-7. A high carbohydrate versus a high monounsaturated fatty acid diet lowers the atherogenic potential of big VLDL particles in patients with type 1 diabetes. Georgopoulos A, Bantle JP, Noutsou M, Hoover HA. “A high (25%) monounsaturated fatty acid (Mono) diet and a high (61%) carbohydrate (CHO) diet were provided for 4 wk in a randomized crossover design to 19 normolipidemic, nonobese patients with type 1 diabetes. The two diets were matched for protein, polyunsaturated/saturated fatty acids, cholesterol and fiber content.” “We conclude that a high CHO diet might be preferable to a high Mono diet, on the basis of the premise that more big VLDL particles could increase the atherosclerotic risk in patients with diabetes.”
J. Girard, "Role of free fatty acids in insulin resistance of subjects with non-insulin-dependent diabetes," Diabetes Metab. 21(2), 79-88, 1995. "Studies performed in the rat suggest that impaired glucose-induced insulin secretion could also be related to chronic exposure of pancreatic beta cells to elevated plasma free fatty acid levels."
Ann Intern Med 1988 May;108(5):663-8. Adverse metabolic effect of omega-3 fatty acids in non-insulin-dependent diabetes mellitus. Glauber H, Wallace P, Griver K, Brechtel G. “Increased interest in using omega-3 fatty acids led us to examine their metabolic effects in six men with type II (non-insulin-dependent) diabetes mellitus. After 1 month of a diet supplemented with these fatty acids, the patients' fasting glucose rose from 13.1 +/- 1.3 to 15.3 +/- 1.3 mmol/L (P = 0.03) and glucose area during a mixed meal profile rose by 22% (P = 0.04).” “After omega-3 fatty acid withdrawal, fasting glucose returned to baseline. Omega-3 fatty acid treatment in type II diabetes leads to rapid but reversible metabolic deterioration, with elevated basal hepatic glucose output and impaired insulin secretion but unchanged glucose disposal rates. Caution should be used when recommending omega-3 fatty acids in type II diabetic persons.”
A. Golay, et al., "Effect of lipid oxidation on the regulation of glucose utilization in obese patients," Acta Diabetologica 32(1), 44-48, 1995. [Free fatty acids strongly and quickly depress the ability to oxidize or store glucose.]
Biol Neonate 1985;47(6):343-9. Increased maternal-fetal transport of fat in diabetes assessed by polyunsaturated fatty acid content in fetal lipids. Goldstein R, Levy E, Shafrir E. The distribution of fatty acids was determined by gas-liquid chromatography in total lipid and triglyceride fraction of extracts of several tissues of streptozotocin-diabetic rats and their fetuses on day 20 of pregnancy. In maternal rats, diabetes did not significantly affect fatty acid distribution apart from small changes in the relative content of linoleate in adipose tissue and liver. In the placenta, the fetal carcass and the fetal liver the triglyceride content increased approximately 2-fold as a result of maternal diabetes, in association with the elevation in triglycerides and free fatty acids in the maternal circulation. A pronounced increase in the relative content of linoleate was recorded in the total lipid and triglyceride extracts of placenta (35 and 59%), fetal carcass (56 and 66%) and fetal liver (100 and 205%). Small increases in arachidonate proportion were also seen in some fetal tissues. The large increase in fetal hepatic linoleate indicates that this tissue is an important uptake target of maternal lipids transported in excess into the fetus. The results confirm the previous observations on increased transplacental fat passage in diabetes by demonstrating that the increment in the essential fatty acid, linoleate, parallels the diabetes-induced triglyceride accumulation in the fetoplacental unit.
A. Gomes, et al., "Anti-hyperglycemic effect of black tea (Camellia sinensis) in rat," J. of Ethnopharmacology 45(3), 223-226, 1995. It "was found to possess both preventive and curative effects on experimentally produced diabetes in rats."
J Endocrinol 2002 Apr;173(1):73-80. Acute effects of fatty acids on insulin secretion from rat and human islets of Langerhans. Gravena C, Mathias PC, Ashcroft SJ. “Long-chain fatty acids (palmitate and stearate) were more effective than medium-chain (octanoate). Saturated fatty acids (palmitate, stearate) were more effective than unsaturated (palmitoleate, linoleate, elaidate).”
Diabetes Metab 2001 Nov;27(5 Pt 2):S12-9. [Modifications in myocardial energy metabolism in diabetic patients]] [Article in French] Grynberg A. “Because FA is the main heart fuel (although the most expensive one in oxygen, and prompt to induce deleterious effects), this process is based on a balanced fatty acid (FA) metabolism. Several pathological situations are associated with an accumulation of FA or derivatives, or with an excessive b-oxidation. The diabetic cardiomyocyte is characterised by an over consumption of FA. The control of the FA/glucose balance clearly appears as a new strategy for cytoprotection, particularly in diabetes and requires a reduced FA contribution to ATP production. Cardiac myocytes can control FA mitochondrial entry, but display weak ability to control FA uptake, thus the fate of non beta-oxidized FA appear as a new impairment for the cell.” “Sudden death, hypercatecholaminemia, diabetes and heart failure have been associated with an altered PUFA content in cardiac membranes.”
Diabetologia 1996 Mar;39(3):251-5. Acceleration of experimental diabetic retinopathy in the rat by omega-3 fatty Acids. Hammes HP, Weiss A, Fuhrer D, Kramer HJ, Papavassilis C, Grimminger F. Omega-3 fatty acids exert several important biological effects on factors that may predispose to diabetic retinopathy. Potential pathogenetic mechanisms include platelet dysfunction, altered eicosanoid production, increased blood viscosity in association with impaired cell deformability and pathologic leucocyte/endothelium interaction. Therefore, we tested whether a 6-month administration of fish oil (750 mg Maxepa, 5 times per week), containing 14% eicosapentaenoic acid (EPA) and 10% docosahexaenic acid, could inhibit the development of experimental retinopathy of the streptozotocin-diabetic rat. The efficiency of fish oil supplementation was evaluated by measuring EPA concentrations in total, plasma and membrane fatty acids and by measuring the generation of lipid mediators (leukotrienes and thromboxanes). Retinal digest preparations were quantitatively analysed for pericyte loss, and the formation of acellular capillaries. Omega-3 fatty acid administration to diabetic rats resulted in a twofold increase of EPA 20:5 in total fatty acids, and a reduction of the thromboxane ratio from 600 (untreated diabetic rats) to 50 (treated diabetic rats). Despite these biochemical changes, diabetes-associated pericyte loss remained unaffected and the formation of acellular, occluded capillaries was increased by 75% in the fish oil treated diabetic group (115.1 +/- 26.8; untreated diabetic 65.2 +/- 15.0 acellular capillary segments/mm2 of retinal area). We conclude from this study that dietary fish oil supplementation may be harmful for the diabetic microvasculature in the retina.
Y. Hattori, et al., "Phorbol esters elicit Ca++-dependent delayed contractions in diabetic rat aorta," Eur. J. Pharmacol. 279(1), 51-58, 1995. [Diabetic tissue is more responsive to activation of protein kinase C by phorbol esters.]
Nutr Metab 1975;18(1):41-8. Adipose tissue metabolism in essential fatty acid deficienty. Effects of prostaglandin e1, epinephrine, and ACTH. Hazinski TA, Barr M, Hertelendy F. In an effort to better define some of the metabolic changes that accompany essential fatty acid deficiency (EFAD), we studied glucose metabolism in adipose tissue of EFAD and normal mice under basal conditions and in the presence of prostaglandin E1 (PGE1), epinephrine, and ACTH1-18. Isolated fat cells were incubated in Krebs-Ringer bicarbonate medium containing glucose 1(-14C) or 6(-14C), and the incorporation of radioactive carbon into CO2, total fat, fatty acids, and glyceride-glycerol was determined. It was found that EFAD increased glucose uptake over controls which could be attributed to increased oxidation to CO2 and fatty acid synthesis. The contribution of the pentose cycle to glucose oxidation was 50-80% higher in EFAD adipocytes as compared to controls. ACTH1-18 (0.1 mug/ml) suppressed this by 18 and 30% in the control and EFAD groups, respectively, while epinephrine decreased pentose cycle activity by 83 and 55% in the two groups, respectively. PGE1 alone had no significant effect, but in combination with epinephrine it abolished the inhibitory action of the catecholamine in both groups.”
J Neurosci Res 1989 Oct;24(2):247-50. Brain mitochondrial swelling induced by arachidonic acid and other long chain free fatty acids. Hillered L, Chan PH. “Polyunsaturated fatty acids (PUFAs), arachidonic acid in particular, are well known, potent inducers of edema in the brain, while monounsaturated and saturated long chain fatty acids do not possess this quality.” “ATP-MgCl2 both prevented and reversed this swelling, while binding of the 20:4 by the addition of bovine serum albumin could only prevent but not reverse the swelling.” “Moreover, reversal of the swelling occurred without recovery of respiratory function.”
J Neurosci Res 1988 Aug;20(4):451-6. Role of arachidonic acid and other free fatty acids in mitochondrial dysfunction in brain ischemia. Hillered L, Chan PH.
B. A. Houssay and C. Martinez, "Experimental diabetes and diet," Science 105, 548-549, 1947. [Mortality was zero on the high coconut oil diet, 100% on the high lard diet. It was 90% on the low protein diet, and 33% on the high protein diet. With a combination of coconut oil and lard, 20%.]
B. A. Houssay, et al., "Accion de la administracion prolongada de glucosa sobre la diabetes de la rata," Rev. Soc. argent. de biol. 23, 288-293, 1947.
S. Ikemoto, et al., "High fat diet-induced hyperglycemia: Prevention by low level expression of a glucose transporter (GLUT4) minigene in transgenic mice," Proc. Nat. Acad. Sci. USA 92(8), 3096-3099, 1995. "...mice fed a high-fat (safflower oil) diet develop defective glycemic control, hyperglycemia, and obesity."
M. Inaba, et al., "Influence of high glucose on 1,25-dihydroxyvitamin D-3-induced effect on human osteoblast-like MG-63 cells," J. Bone Miner. Res. 10(7), 1050-1056, 1995.
J. S. Jensen, et al., "Microalbuminuria reflects a generalized transvascular albumin leakiness in clinically healthy subjects," Clin. Sci. 88(6), 629-633, 1995.
J Am Geriatr Soc 1984 May;32(5):375-9. Low triiodothyronine and raised reverse triiodothyronine levels in patients over fifty years of age who have type II diabetes mellitus: influence of metabolic control, not age. Kabadi UM, Premachandra BN. “Several studies have demonstrated that the uncontrolled diabetic state in both type I as well as type II diabetes mellitus is characterized by altered thyroid hormone metabolism, which results in the lowering of serum triiodothyronine (T3) levels and a reciprocal elevation of T3 (rT3) levels.” “Serum T3 levels declined and rT3 levels rose in the diabetic patients with worsening of the metabolic control.”
Metabolism 1989 Mar;38(3):278-81. The effect of fatty acids on the vulnerability of lymphocytes to cortisol. Klein A, Bruser B, Malkin A. “We have shown previously that cortisol-sensitive lymphocytes (thymocytes) have a much lower capacity than cortisol-resistant cells to catabolize cortisol and that linoleic acid inhibits the catabolism of cortisol by lymphocytes and modulates the sensitivity of lymphocytes to cortisol.” “Measuring the effect of fatty acids on cortisol catabolism by lymphocytes indicated that the polyunsaturated fatty acids, linoleate, arachidonate, and eicosapentaenoic, inhibit cortisol catabolism by lymphocytes.” “Examining the effect of fatty acids on the vulnerability of lymphocytes to cortisol, we noted that saturated fatty acids had no significant effect, whereas the aforementioned polyunsaturated fatty acids make lymphocytes more sensitive to cortisol.”
Jpn J Pharmacol 1978 Apr;28(2):277-87. Relationship between cerebral energy failure and free fatty acid accumulation following prolonged brain ischemia. Kuwashima J, Nakamura K, Fujitani B, Kadokawa T, Yoshida K, Shimizu M. “Mitochondria isolated from the ischemic brain showed an impairment of oxidative phosphorylation. The ischemic brain was also characterized by remarkable accumulation of free fatty acids known to have properties as an uncoupling factor.” “These results indicate that cerebral energy failure in the ischemic brain is related to the accumulation of free fatty acids, which are derived from endogenous brain lipids.”
Probl Endokrinol (Mosk) 1992 Nov-Dec; 38(6):53-4. [Effect of protein content in rat diet on water-soluble vitamin metabolism in streptozotocin-induced diabetes] [Article in Russian] Kodentsova VM, Sadykova RE, Dreval' AV, Vrzhesinskaia OA, Sokol'nikov AA, Beketova NA. Water-soluble group B vitamins metabolism was studied over the course of streptozotocin-induced diabetes mellitus in rats fed semisynthetic isocaloric diets containing 18 and 50% of protein. A high-protein diet in diabetes mellitus does not influence riboflavin metabolism disordered in this disease but reduced 4-pyridoxyl acid excretion to the level characteristic of healthy animals. The observed trend to an increase of liver nicotinamide coenzymes levels and of 1-methylnicotinamide urinary excretion reflects increased niacin synthesis from the diet protein tryptophan, for niacin level is reduced in diabetes.
M. Kusunoki, et al., "Amelioration of high fat feeding-induced insulin resistance in skeletal muscle with the antiglucocorticoid RU486," Diabetes 44(6), 718-720, 1995. "These results suggest that glucocorticoids play, in a tissue-specific manner, a role in the maintenance and/or production of insulin resistance produced by high-fat feeding."
J Neuroendocrinol 2001 Sep;13(9):827-35. A new perspective on glucocorticoid feedback: relation to stress, carbohydrate feeding and feeling better. Laugero KD. “In this review, I discuss findings that have led us to view glucocorticoid feedback in the HPA axis in a new light. Much of what has precipitated this view comes from a very surprising finding in our laboratory; sucrose ingestion normalizes feeding, energy balance and central corticotropin releasing factor expression in adrenalectomized (ADX) rats.” “Taken together, recent findings of the well-known importance of glucocorticoids to feeding and energy balance, and the modulatory actions of carbohydrate ingestion on both basal and stress-induced activity in the HPA axis, strongly suggest that many metabolic (e.g. obesity) and psychological (e.g. depression) pathologies, which often present together and have been associated with stress and HPA dysregulation, might, in part, be understood in light of our new view of glucocorticoid feedback.”
Endocrinology 2001 Jul;142(7):2796-804. Sucrose ingestion normalizes central expression of corticotropin-releasing-factor messenger ribonucleic acid and energy balance in adrenalectomized rats: a glucocorticoid-metabolic-brain axis? Laugero KD, Bell ME, Bhatnagar S, Soriano L, Dallman MF. “Both CRF and norepinephrine (NE) inhibit food intake and stimulate ACTH secretion and sympathetic outflow. CRF also increases anxiety; NE increases attention and cortical arousal. Adrenalectomy (ADX) changes CRF and NE activity in brain, increases ACTH secretion and sympathetic outflow and reduces food intake and weight gain; all of these effects are corrected by administration of adrenal steroids. Unexpectedly, we recently found that ADX rats drinking sucrose, but not saccharin, also have normal caloric intake, metabolism, and ACTH.” “Voluntary ingestion of sucrose restores CRF and dopamine-beta-hydroxylase messenger RNA expression in brain, food intake, and caloric efficiency and fat deposition, circulating triglyceride, leptin, and insulin to normal.”
A. Lazarow, "Protection against alloxan diabetes," Anat. Rec. 97, 353, 1947.
A. Lazarow, "Protective effect of glutathione and cysteine against alloxan diabetes in the rat," Proc. Soc. Exp. Biol. & Med. 61, 441-447, 1946. [While certain doses of cysteine, glutathione, and thioglycolic acid completely prevented alloxan diabetes, it was interesting that all of the rats receiving ascorbic acid became diabetic. To me, this argues for the free radical cause of diabetes, rather than just the sulfhydryl oxidation. Lazarow suggested that succinic dehydrogenase, and various other sulfhydryl enzymes, including those involved in fatty acid oxidation, might be involved.]
Minerva Endocrinol 1990 Oct-Dec;15(4):273-7. [Postprandial thermogenesis and obesity: effects of glucose and fructose]. [Article in Italian] Macor C, De Palo C, Vettor R, Sicolo N, De Palo E, Federspil G. “Energy expenditure was calculated both in basal conditions and during the test (resting metabolic rate: RMR) using indirect calorimetry expressed per kg of lean weight, as assessed using bioimpedance measurement techniques. Blood samples were collected to assay glycemia and insulinemia. Results show that increased RMR induced by glucose was significantly reduced in the group of obese subjects compared to controls. In the same group of obese subjects, RMR was found to be significantly higher following fructose in comparison to the glucose response but did not differ from that in controls. Data confirm the existence of reduced thermogenesis in obese subjects induced by glucose. The fact that this phenomenon was not recorded in the same subjects following the fructose tolerance test, whose metabolism is insulin-independent, supports the hypothesis that reduced glucose-induced thermogenesis in obese subjects may depend on insulin resistance.”
Diabetes Care 2000 Oct;23(10):1472-7. Dietary unsaturated fatty acids in type 2 diabetes: higher levels of postprandial lipoprotein on a linoleic acid-rich sunflower oil diet compared with an oleic acid-rich olive oil diet. Madigan C, Ryan M, Owens D, Collins P, Tomkin GH.
Proc Natl Acad Sci U S A 1990 Nov;87(22):8845-9. Incorporation of marine lipids into mitochondrial membranes increases susceptibility to damage by calcium and reactive oxygen species: evidence for enhanced activation of phospholipase A2 in mitochondria enriched with n-3 fatty Acids. Malis CD, Weber PC, Leaf A, Bonventre JV. “Mitochondrial site 1 (NADH coenzyme Q reductase) activity was reduced to 45 and 85% of control values in fish-oil- and beef-tallow-fed groups, respectively. Exposure to Ca2+ and reactive oxygen species enhance the release of polyunsaturated fatty acids enriched at the sn-2 position of phospholipids from mitochondria of fish-oil-fed rats when compared with similarly treated mitochondria of beef-tallow-fed rats.” “Phospholipase A2 activity and mitochondrial damage are enhanced when mitochondrial membranes are enriched with n-3 fatty acids.”
FEBS Lett 1998 Oct 16:437(1-2):24-8. Generation of protein carbonyls by glycoxidation and lipoxidation reactions with autoxidation products of ascorbic acid and polyunsaturated fatty acids. Miyata T, Inagi R, Asahi K, Yamada Y, Horie K, Sakai H, Uchida K, Kurokawa K. “In vitro incubation of proteins with ascorbic acid accelerated the production of protein carbonyls as well as CML and pentosidine, and incubation with arachidonate accelerated the production of protein carbonyls as well as CML, MDA, and HNE. By contrast, incubation of proteins with glucose resulted in the production of CML and pentosidine, but not protein carbonyls.” “The present study suggests that ascorbate and polyunsaturated fatty acids, but not glucose, represent potential sources of protein carbonyls, and that both the glycoxidation and lipoxidation reactions contribute to protein carbonyl formation in aging and various diseases.”
Chem Phys Lipids 1996 Jan 25;79(1):47-53. Previously unknown aldehydic lipid peroxidation compounds of arachidonic acid. Mlakar A, Spiteller G. Lehrstuhl fr Organische Chemie I, “Arachidonic acid was oxidized by iron ascorbate.” “The main aldehydic lipid peroxidation product was found to be the well-known 4-hydroxy-2-nonenal (HNE), but 2-hydroxy heptanal (HH) -- a previously unknown lipid peroxidation product of arachidonic acid -- was detected to be nearly equally abundant. Malondialdehyde (MDA), glyoxal and 2-hydroxy-4-decenal (HDE) were detected to be produced in up to 100 times lower amounts compared to HNE.”. . . . “Since this and analogous hydroxy acids (LOHs) are the main biological degradation products of hydroperoxides of unsaturated acids (LOOHs) their further peroxidation seems to be a main source of toxic aldehydes.”
J Clin Endocrinol Metab 2000 Dec;85(12):4515-9. Acute fructose administration decreases the glycemic response to an oral glucose tolerance test in normal adults. Moore MC, Cherrington AD, Mann SL, Davis SN. “In animal models, a small (catalytic) dose of fructose administered with glucose decreases the glycemic response to the glucose load.” “In conclusion, low dose fructose improves the glycemic response to an oral glucose load in normal adults without significantly enhancing the insulin or triglyceride response. Fructose appears most effective in those normal individuals who have the poorest glucose tolerance.”
Tumour Biol 1988;9(5):225-32. Modulation of cell-mediated immune response by steroids and free fatty acids in AIDS patients: a critical survey. Nunez EA. “The overall data presented in this review show that cortisol and free fatty acids, in particular long-chain polyunsaturated fatty acids, each have immunoinhibitory properties on lymphoblastic transformation of certain T lymphocytes. This effect is enhanced when the two factors are associated. These data could explain in part the immunosuppression observed in acquired immunodeficiency syndrome (AIDS) patients where enhanced concentrations of cortisol and polyunsaturated fatty acids have been observed.” “These new weapons could be the administration of diets or treatments (liposomes) modifying the lipid profile of circulating cells and/or viruses and the utilization of hormonal therapy in AIDS and in some types of cancer which often present a biologic picture similar to that of AIDS.”
Diabetes Care 1984 Sep-Oct;7(5):465-70. Effect of protein ingestion on the glucose and insulin response to a standardized oral glucose load. Nuttall FQ, Mooradian AD, Gannon MC, Billington C, Krezowski P. “The plasma glucose area above the baseline following a glucose meal was reduced 34% when protein was given with the glucose.” “The insulin area following glucose was only modestly greater than with a protein meal (97 +/- 35, 83 +/- 19 microU X h/ml, respectively).” “When various amounts of protein were given with 50 g glucose, the insulin area response was essentially first order. Subsequently, subjects were given 50 g glucose or 50 g glucose with 50 g protein as two meals 4 h apart in random sequence. The insulin areas were not significantly different for each meal but were higher when protein + glucose was given. After the second glucose meal the plasma glucose area was 33% less than after the first meal. Following the second glucose + protein meal the plasma glucose area was markedly reduced, being only 7% as large as after the first meal. These data indicate that protein given with glucose will increase insulin secretion and reduce the plasma glucose rise in at least some type II diabetic persons.” Randomized Controlled Trial
Biochem J 1985 Sep 1;230(2):329-37. Inhibitory effects of some long-chain unsaturated fatty acids on mitochondrial beta-oxidation. Effects of streptozotocin-induced diabetes on mitochondrial beta-oxidation of polyunsaturated fatty acids. Osmundsen H, Bjornstad K. “Evidence showing that some unsaturated fatty acids, and in particular docosahexaenoic acid, can be powerful inhibitors of mitochondrial beta-oxidation is presented. This inhibitory property is, however, also observed with the cis- and trans-isomers of the C18:1(16) acid. Hence it is probably the position of the double bond(s), and not the degree of unsaturation, which confers the inhibitory property. It is suggested that the inhibitory effect is caused by accumulation of 2,4-di- or 2,4,7-tri-enoyl-CoA esters in the mitochondrial matrix.”
Free Radic Biol Med 1999 Oct;27(7-8):901-10. Thyroid status modulates glycoxidative and lipoxidative modification of tissue Proteins. Pamplona R, Portero-Otin M, Ruiz C, Bellmunt MJ, Requena JR, Thorpe SR, Baynes JW, Romero M, Lopez-Torres M, Barja G. Steady state protein modification by carbonyl compounds is related to the rate of carbonyl adduct formation and the half-life of the protein. Thyroid hormones are physiologic modulators of both tissue oxidative stress and protein degradation. The levels of the glycation product N(epsilon)-fructoselysine (FL) and those of the oxidation products, N(epsilon)-(carboxymethyl)lysine (CML) and malondialdehyde-lysine (MDA-lys), identified by GC/MS in liver proteins, decreased significantly in hyperthyroid rats, as well as (less acutely) in hypothyroid animals. Immunoblotting of liver proteins for advanced glycation end-products (AGE) is in agreement with the results obtained by GC/MS. Cytosolic proteolytic activity against carboxymethylated foreign proteins measured in vitro was significantly increased in hypo- and hyperthyroidism. Oxidative damage to DNA, estimated as 8-oxo-7,8-dihydro-2'-deoxyguanosine (8oxodG), did not show significant differences between groups. The results suggests that the steady state levels of these markers depend on the levels of thyroid hormones, presumably through their combined effects on the rates of protein degradation and oxidative stress, whereas DNA is more protected from oxidative damage.
Metabolism 1999 Mar;48(3):406-9. The blood vessel, linchpin of diabetic lesions. Plante GE, Alfred J, Chakir M. “The morbidity and mortality associated with diabetes mellitus are essentially related to the vascular lesions that develop over time in this condition. Both the macrocirculation and microcirculation are involved, and as a consequence, vital organs such as the brain, retina, heart, and kidney and the limbs become damaged.” “Changes in the structure of conduit arteries, partly responsible for the alteration in compliance characteristics, could well be related to the way these arteries are fed by the vasa vasorum system.” “Preliminary results indicate that the size of terminal arterioles of the vasa vasorum (increased diameter) and the capillary permeability to albumin (markedly enhanced) in this specialized network are profoundly affected in the thoracic aorta obtained from diabetic animals. Albumin extravasation into the interstitial fluid compartment of the aorta is likely to lead to structural and physicochemical changes: in fact, removal of interstitial macromolecules via lymphatic drainage is poor in the blood vessel wall of large arteries.”
Metabolism 2001 Dec;50(12):1472-8. Serum phospholipid fatty acid composition and insulin action in type 2 diabetic patients. Pelikanova T, Kazdova L, Chvojkova S, Base J. “Increased contents of highly unsaturated n-6 family FA (P <.01), arachidonic acid in particular . . . were found in all groups of diabetics compared with HS [healthy subjects], while lower levels of linoleic acid were seen in DMN (P <.001) and DMH (P <.05). The contents of saturated FA and monounsaturated FA were comparable in HS, DMN, and DMD.”
J Clin Invest 2002 Mar;109(6):805-15. Acute intensive insulin therapy exacerbates diabetic blood-retinal barrier breakdown via hypoxia-inducible factor-1alpha and VEGF. Poulaki V, Qin W, Joussen AM, Hurlbut P, Wiegand SJ, Rudge J, Yancopoulos GD, Adamis AP. “Here we demonstrate that acute intensive insulin therapy markedly increases VEGF mRNA and protein levels in the retinae of diabetic rats.” “Blood-retinal barrier breakdown is markedly increased with acute intensive insulin therapy. . . .” “To our knowledge, these data are the first to identify a specific mechanism for the transient worsening of diabetic retinopathy, specifically blood-retinal barrier breakdown, that follows the institution of intensive insulin therapy.”
Acta Endocrinol (Copenh) 1992 Apr;126(4):378-80. Lipid peroxidation in early experimental diabetes in rats: effects of diabetes and insulin. Rungby J, Flyvbjerg A, Andersen HB, Nyborg K. “In the kidney, lipid peroxidation was increased after one week of diabetes; insulin treatment reduced the level of lipid peroxidation to levels lower than seen in controls. In the liver, diabetes caused an increased lipid peroxidation, which could be reversed by insulin; no additional effect of insulin was found. In heart and pancreas no effects of diabetes or insulin were demonstrated. The present paper provides evidence that lipid peroxidation is increased in the early stages of experimental diabetes and is reversible by insulin treatment. Hyperinsulinaemia may, in itself, counteract lipid peroxidation in kidney.”
Br J Nutr 1997 Sep;78(3):459-67. Influence of dietary protein and fat on serum lipids and metabolism of essential fatty acids in rats. Ratnayake WM, Sarwar G, Laffey P. A “In general, the concentrations of serum triacylglycerols and total cholesterol and liver phospholipid levels of arachidonic acid (AA) and docosahexaenoic acid (DHA) were higher in rats fed on casein diets compared with those fed on the gelatin diets. These effects were more pronounced in rats fed on the high-casein (300 g/kg)-high-fat (150 g/kg) diet. Gelatin was hypocholesterolaemic and also suppressed the liver phospholipid levels of AA and DHA (reported for the first time). The difference in the amino acid composition between casein and gelatin may be responsible for the observed effects. Casein contains higher levels of glutamic acid, methionine, phenylalanine and tyrosine, while gelatin contains higher levels of arginine, glycine and hydroxyproline.”
Br Med J 1979 Jun 30;1(6180):1753-6. Improved glucose control in maturity-onset diabetes treated with high-carbohydrate-modified fat diet. Simpson RW, Mann JI, Eaton J, Moore RA, Carter R, Hockaday TD. “Fourteen patients with established maturity-onset diabetes were treated as outpatients with a high-carbohydrate-(about 60% of total daily energy requirements)-modified fat diet (ratio of polyunsaturated fatty acids to other fatty acids greater than or equal to 1:1) for six weeks.” “The findings suggest that it is no longer justifiable to prescribe a low-carbohydrate diet for maturity-onset diabetes.”
Postgrad Med J 1981 Aug;57(670):511-5. Severe hypertriglyceridaemia responding to insulin and nicotinic acid therapy. Smith SR. “Treatment with insulin and restriction of dietary carbohydrate led to a 50% reduction in the triglyceride concentration, and the addition of nicotinic acid in modest doses led ultimately to a complete normalization of the patient's lipid values. A close correlation was noted between the falling triglyceride concentration and the rising serum sodium concentration during the course of successful therapy. Overall, it is felt likely that this patient's severe and reversible hypertriglyceridaemia was on the basis of excessively rapid lipolysis leading to high concentrations of very low density lipoprotein production.”
Am J Clin Nutr 1993 Nov;58(5 Suppl):766S-770S. Fructose and dietary thermogenesis. Tappy L, Jequier E. “Fructose ingestion induces a greater thermogenesis than does glucose. This can be explained by the hydrolysis of 3.5-4.5 mol ATP/mol fructose stored as glycogen, vs 2.5 mol ATP/mol glucose stored. Therefore the large thermogenesis of fructose corresponds essentially to an increase in obligatory thermogenesis. Obese individuals and obese patients with non-insulin-dependent diabetes mellitus commonly have a decrease in glucose-induced thermogenesis. These individuals in contrast display a normal thermogenesis after ingestion of fructose. This may be explained by the fact that the initial hepatic fructose metabolism is independent of insulin.”
Diabetes 2002 Jun;51(6):1772-8. Inhibition of interleukin-1beta-induced COX-2 and EP3 gene expression by sodium salicylate enhances pancreatic islet beta-cell function. Tran PO, Gleason CE, Robertson RP.
Proc Natl Acad Sci U S A 1998 Apr 28;95(9):4882-7. Protein-bound acrolein: potential markers for oxidative stress. Uchida K, Kanematsu M, Sakai K, Matsuda T, Hattori N, Mizuno Y, Suzuki D, Miyata T, Noguchi N, Niki E, Osawa T. “Acrolein (CH2==CH---CHO) is known as a ubiquitous pollutant in the environment. Here we show that this notorious aldehyde is not just a pollutant, but also a lipid peroxidation product that could be ubiquitously generated in biological systems. Upon incubation with BSA, acrolein was rapidly incorporated into the protein and generated the protein-linked carbonyl derivative, a putative marker of oxidatively modified proteins under oxidative stress.” “Immunohistochemical analysis of atherosclerotic lesions from a human aorta demonstrated that antigenic materials recognized by mAb5F6 indeed constituted the lesions, in which intense positivity was associated primarily with macrophage-derived foam cells and the thickening neointima of arterial walls. The observations that (i) oxidative modification of low-density lipoprotein with Cu2+ generated the acrolein-low-density lipoprotein adducts and (ii) the iron-catalyzed oxidation of arachidonate in the presence of protein resulted in the formation of antigenic materials suggested that polyunsaturated fatty acids are sources of acrolein that cause the production of protein-bound acrolein. These data suggest that the protein-bound acrolein represents potential markers of oxidative stress and long-term damage to protein in aging, atherosclerosis, and diabetes.”
J Intern Med 1990 Aug;228(2):165-71. Dietary supplementation with n-3 fatty acids may impair glucose homeostasis in patients with non-insulin-dependent diabetes mellitus. Vessby B, Boberg M. “The blood glucose concentration tended to increase during MaxEPA treatment, and to decrease during the placebo period, the changes under the two regimes being significantly different (P less than 0.01). In addition, the rate constant for glucose disappearance (k value) for the intravenous insulin-tolerance test, which reflected the peripheral insulin sensitivity, tended to decrease during MaxEPA treatment and increase during administration of the placebo, there being a significant difference (P less than 0.03) between the changes during the two treatments. The reason for the observed changes in blood glucose concentration and peripheral insulin sensitivity is still unclear.”
Diabet Med 1992 Mar;9(2):126-33. Polyunsaturated fatty acids may impair blood glucose control in type 2 diabetic Patients. Vessby B, Karlstrom B, Boberg M, Lithell H, Berne C. “Average blood glucose concentrations during the third week were significantly higher fasting (+15%, p less than 0.01), and during the day at 1100 h (+18%, p less than 0.001) and 1500 h (+17%, p = 0.002) on PUFA than on the saturated fat diet.”
Drugs 1999;58 Suppl 1:31-9; discussion 75-82. The antihyperglycaemic effect of metformin: therapeutic and cellular mechanisms. Wiernsperger NF, Bailey CJ “Other effects involved in the blood glucose-lowering effect of metformin include an insulin-independent suppression of fatty acid oxidation and a reduction in hypertriglyceridaemia. These effects reduce the energy supply for gluconeogenesis and serve to balance the glucose-fatty acid (Randle) cycle.”
J Biol Chem 2001 Mar 30;276(13):9800-7. Polyunsaturated fatty acids suppress hepatic sterol regulatory element-binding protein-1 expression by accelerating transcript decay. Xu J, Teran-Garcia M, Park JH, Nakamura MT, Clarke SD. “Our initial studies indicated that the induction of SREBP-1 expression by insulin and glucose was blocked by PUFA. Nuclear run-on assays suggested PUFA reduced SREBP-1 mRNA by post-transcriptional mechanisms.” “Although the mechanism by which PUFA accelerate SREBP-1 mRNA decay remains to be determined, cloning and sequencing of the 3'-untranslated region for the rat SREBP-1 transcript revealed the presence of an A-U-rich region that is characteristic of a destablizing element.”
Recent Adv Stud Cardiac Struct Metab 1976 May 26-29;12:271-7. Arrhythmogenic effects of acute free fatty acid mobilization on ischemic heart. Yamazaki N, Suzuki Y, Kamikawa T, Ogawa K, Mizutani K, Kakizawa N, Yamamoto M.
Science 1978 Jul 28;201(4353):358-60. Brain edema: induction in cortical slices by polyunsaturated fatty acids. Chan PH, Fishman RA The presence of polyunsaturated and saturated fatty acids in leukocytic membranes prompted study of their possible role in the induction of brain edema. Polyunsaturated fatty acids including sodium arachidonate, sodium linoleate, sodium linolenate, and docasahexaenoic acids induced edma in slices of rat brain cortex. This cellular edema was specific, since neither saturated fatty acids nor a fatty acid containing a single double bond had such effect.
J Neurochem 1986 Oct;47(4):1181-9. Effects of arachidonic acid on glutamate and gamma-aminobutyric acid uptake in primary cultures of rat cerebral cortical astrocytes and neurons. Yu AC, Chan PH, Fishman RA. “Arachidonic acid inhibited glutamate uptake in both astrocytes and neurons. The inhibitory effect was observed within 10 min of incubation with arachidonic acid and reached approximately 80% within 120 min in both types of culture. The arachidonic acid effect was not only time-dependent, but also dose-related. Arachidonic acid, at concentrations of 0.015 and 0.03 mumol/mg protein, significantly inhibited glutamate uptake in neurons, whereas 20 times higher concentrations were required for astrocytes. The effects of arachidonic acid were not as deleterious on GABA uptake as on glutamate uptake in both astrocytes and neurons.” “Other polyunsaturated fatty acids, such as docosahexaenoic acid, affected amino acid uptake in a manner similar to arachidonic acid in both astrocytes and neurons. However, saturated fatty acids, such as palmitic acid, exerted no such effect.”