Onset and evolution of nephropathy in rats with spontaneous diabetes mellitus.

The occurrence of renal diabetic complications was studied in diabetic nonobese IIM/FmeSS (eSS) rats. The results were compared with eumetabolic Wistar rats paired by sex and age. Between 6 and 12 months of age, eSS male rats had higher fructosamine values and glucose intolerance as well as increasing proteinuria and uremia. Enhancement in water, calcium and phosphorus fractional excretion with a concomitant lower sodium excretion, was observed from 12 months of age on. 18- and 21-month-old eSS rats exhibited fasting hyperglycaemia and rising values of fructosamine, glucose intolerance and glycosuria. Simultaneously, a notorious worsening of proteinuria as well as alterations in glomerular filtration were verified. Optic microscopy of 12-month-old eSS rat kidneys showed areas of tubular dilatation with protein cylinders. In 21-month-old eSS animals, kidneys appeared overtly damaged. Increased capsular, glomerular and Henle's thin loop diameters were verified in 12- and 21-month-old eSS rats. Glomeruli showed diffuse hypertrophy of mesangial tissue and thickening of the basement membrane. Areas of markedly atrophic and dilated tubules containing acidophilic proteinaceous material were observed. At age of 21 months, kidneys of eumetabolic Wistar control rats presented foci of interstitial and pielic inflammatory infiltrates.

Influence of gonadectomy in eSS diabetic rats.

The influence of gonadectomy on some variables related to the diabetic syndrome was studied in the eSS line of rats, a nonobese model of spontaneous non-insulin-dependent diabetes, whose biochemical and histopathological manifestations are more severe in males than in females. Rats were gonadectomized at 90 days of age. Spayed animals showed higher body weight, impaired intolerance to glucose at 9 and 12 months of age, lower insulinemia and a decreased number of large pancreatic islets. Castrated rats revealed lower body weight when compared with controls. However, those males did not evidence impairment in the intolerance to glucose, changes insulinemia or remarkable modifications in endocrine pancreas histology. In kidneys, a lower cellular area in superficial proximal convoluted tubules was noticed. Despite the lower biomass registered in orchidectomized animals, their diabetic evolution was not modified. Conversely, ovariectomy appeared to be a worsening factor.

Effects of dietary sucrose option on the diabetic syndrome of the eSS rat.

The eSS rat is a model of human spontaneous non-insulin-dependent diabetes. Male eSS rats were divided at the age of 4 months into two groups (eSSA and eSSB), both receiving the usual commercial balanced diet with sucrose also made available to eSSA. Sucrose intake did not imply a higher caloric diet, and no differences were found between groups in body weight and plasma triglyceride levels from 6 to 12 months of age. Sucrose option resulted in lower protein, lipid and carbohydrate intakes in eSSA animals. Plasma glucose values were higher in eSSA at different times of the tolerance curve. Likewise, eSSA kidneys showed significantly higher capsular and glomerular diameters and there was a discrete PAS-positive thickening of their basement membrane. We conclude that prolonged ad libitum sucrose intake, without weight gain, causes a moderate metabolic impairment and renal lesions in the eSS diabetic rat.

[Relationship of diet, biomass and expression of diabetes in eSS rats]. / Relación entre dieta, biomasa y expresión de la diabetes en la rata eSS.

The long-term effect of feeding eSS rats three commercial diets on the development of diabetes and its complications has been investigated. These diets differ in their proportions of carbohydrates, fibres, lipids and proteins: diet A is rich in lipids, B in carbohydrates and fibres and C in proteins. However, the proportions of these components lie within the range recommended for rats. Animals receiving diet C showed the highest growth rate and were the first to develop diabetes at the age of four months. They had, moreover, the highest levels of triglycerides, total cholesterol and HDL-cholesterol. Animals fed the A diet were heavier than the other groups at 13 months of age, showing a diabetic glucose tolerance test and the highest values of circulating insulin. They were already diabetic when tested at the age of 6 months. The group fed the B diet remained leaner than the other groups and free of diabetes up to the test performed when they were ten months old. The findings at the age of 23 months were: the A animals developed the largest retroperitoneal and epididymal adipose tissue masses, the C group was the most affected by cataracts which were total, and bilateral in some cases, whereas the B rats were free of them and the A animals showed milder lesions than the C rats. Histological studies of pancreas and kidneys demonstrated that the C animals had fewer Langerhans islands than the other groups and the most severe renal lesions while the B animals had no renal damage. It is concluded that diets leading to overweight, particularly those rich in proteins, make the diabetic syndrome worse in eSS rats.

Relacion entre dieta, biomasa y expresion de la diabetes en la rata eSS / Relation between diet, body mass and expression of diabetes in eSS rats

Se valoró el efecto a largo plazo de alimentar ratras machos eSS desde el destete con tres dietas comerciales: de más alto contenido de grasas (A), de glúcidos y fibras (B) y de proteínas (C). Los animales C, de mayor crecimiento, alcanzaron la categoría de diabéticos a los 4 meses, presentando los valores más latos de triglicéridos, colesterol total y HDL-colesterol. Los A, diabéticos desde los 6 meses, tuvieron más elevado el peso, la glucemia tras sobrecarga glúcida y la insulenemia a partir de los 13 meses. Los B, de menor peso, no expresaron la diabetes hasta los 10 meses. Los animales A mostraron a los 23 meses paquetes adiposos retroperitoneal y epididmatrios de más peso, en tanto que el grupo C presentó cataratas totales y bilaterales. En A las cataratas fueron menos graves y B no las mostró. El examen histológico reveló en C menor número de islotes de Langerhans y lesiones renales ms intensas. No se comprobó daño renal en B. Se concluye que dietas ricas en proteínas y grasas que inducen mayor peso constituyen factores agravantes de la diabetes eSS mientras que una dieta con menor densidad calórica y abundante en fibra retarda su comienzo

Relación entre dieta, biomasa y expresión de la diabetes en la rata eSS. / [Relationship of diet, biomass and expression of diabetes in eSS rats]

The long-term effect of feeding eSS rats three commercial diets on the development of diabetes and its complications has been investigated. These diets differ in their proportions of carbohydrates, fibres, lipids and proteins: diet A is rich in lipids, B in carbohydrates and fibres and C in proteins. However, the proportions of these components lie within the range recommended for rats. Animals receiving diet C showed the highest growth rate and were the first to develop diabetes at the age of four months. They had, moreover, the highest levels of triglycerides, total cholesterol and HDL-cholesterol. Animals fed the A diet were heavier than the other groups at 13 months of age, showing a diabetic glucose tolerance test and the highest values of circulating insulin. They were already diabetic when tested at the age of 6 months. The group fed the B diet remained leaner than the other groups and free of diabetes up to the test performed when they were ten months old. The findings at the age of 23 months were: the A animals developed the largest retroperitoneal and epididymal adipose tissue masses, the C group was the most affected by cataracts which were total, and bilateral in some cases, whereas the B rats were free of them and the A animals showed milder lesions than the C rats. Histological studies of pancreas and kidneys demonstrated that the C animals had fewer Langerhans islands than the other groups and the most severe renal lesions while the B animals had no renal damage. It is concluded that diets leading to overweight, particularly those rich in proteins, make the diabetic syndrome worse in eSS rats.

Relacion entre dieta, biomasa y expresion de la diabetes en la rata eSS / Relation between diet, body mass and expression of diabetes in eSS rats

Se valoró el efecto a largo plazo de alimentar ratras machos eSS desde el destete con tres dietas comerciales: de más alto contenido de grasas (A), de glúcidos y fibras (B) y de proteínas (C). Los animales C, de mayor crecimiento, alcanzaron la categoría de diabéticos a los 4 meses, presentando los valores más latos de triglicéridos, colesterol total y HDL-colesterol. Los A, diabéticos desde los 6 meses, tuvieron más elevado el peso, la glucemia tras sobrecarga glúcida y la insulenemia a partir de los 13 meses. Los B, de menor peso, no expresaron la diabetes hasta los 10 meses. Los animales A mostraron a los 23 meses paquetes adiposos retroperitoneal y epididmatrios de más peso, en tanto que el grupo C presentó cataratas totales y bilaterales. En A las cataratas fueron menos graves y B no las mostró. El examen histológico reveló en C menor número de islotes de Langerhans y lesiones renales ms intensas. No se comprobó daño renal en B. Se concluye que dietas ricas en proteínas y grasas que inducen mayor peso constituyen factores agravantes de la diabetes eSS mientras que una dieta con menor densidad calórica y abundante en fibra retarda su comienzo (AU)

Spontaneous diabetes in eSS rats.

A spontaneous non-insulin-dependent diabetes in a highly inbred line of rats called eSS has been described. It is characterized by early impaired glucose tolerance worsening with age. Males are far more severely affected than females. These animals also exhibit hypertriglyceridemia and hypercholesterolemia. In spite of their hyperglycemia, eSS males have an excess of circulating plasma insulin compared with alpha controls. Eight-month-old eSS males were sensitive to exogenous insulin. Moreover, as the plasma insulin values decrease with age, glucose tolerance is further impaired. An improvement in the metabolic disturbances was registered in diabetic eSS males under long-term food deprivation. Histopathological examination of the pancreas revealed marked changes compared with age-matched controls. The pancreatic islet structure looked disrupted and islets became smaller and more scattered with advancing age. A diffuse glomerulosclerosis, interstitial lymphocyte infiltrates and tubular nephrosis were present in kidneys.

Efecto del ambiente nutricional sobre la expresión del sindrome diabético de las ratas eSS / Effect of the nutricional environment on the expression of the eSS rat diabetic syndrome

La expresión del genotipo diabético está ampliamente influida, tanto en el hombre como en algunos modelos murinos, por el ambiente nutricional . En este trabajo se ha estudiado la biomasa, el CMDr y la tolerancia glúcida en ratas de la línea diabética eSS alimentadas con una dieta balanceada (eSS1) y con una mezcla de alimentos naturales de menor contenido proteico (eSS2). eSS1 alcanzó a los 6 meses mayor peso corporal (p<0,01) y expresó más intolerancia glúcida (p<0,01) mientras que ambos grupos tuvieron menor CMDr que la línea alfa control. Con tres semanas de restricción calórica eSS1 y eSS2 disminuyeron su hiperglucemia llegando eSS2 a cifras casi normales. La adaptación de ambos a la menor ingesta fue superior a la de alfa, que perdió un 8% de su biomasa. eSS1 y eSS2 no difieren en el número y tamaño de los islotes de Langerhans ni respecto del peso relativo del páncreas. A los 9 meses eSS1 requirió 5 semanas para disminuir la hiperglucemia y esta respuesta se acompañó de una importante pérdida de biomasa. Se concluye que el genotipo eSS se desempeña mejor en ambientes "pobres" y que el efecto beneficioso de la restricción calórica se enmascara en animales de más edad

Efecto del ambiente nutricional sobre la expresión del sindrome diabético de las ratas eSS / Effect of the nutricional environment on the expression of the eSS rat diabetic syndrome

La expresión del genotipo diabético está ampliamente influida, tanto en el hombre como en algunos modelos murinos, por el ambiente nutricional . En este trabajo se ha estudiado la biomasa, el CMDr y la tolerancia glúcida en ratas de la línea diabética eSS alimentadas con una dieta balanceada (eSS1) y con una mezcla de alimentos naturales de menor contenido proteico (eSS2). eSS1 alcanzó a los 6 meses mayor peso corporal (p<0,01) y expresó más intolerancia glúcida (p<0,01) mientras que ambos grupos tuvieron menor CMDr que la línea alfa control. Con tres semanas de restricción calórica eSS1 y eSS2 disminuyeron su hiperglucemia llegando eSS2 a cifras casi normales. La adaptación de ambos a la menor ingesta fue superior a la de alfa, que perdió un 8% de su biomasa. eSS1 y eSS2 no difieren en el número y tamaño de los islotes de Langerhans ni respecto del peso relativo del páncreas. A los 9 meses eSS1 requirió 5 semanas para disminuir la hiperglucemia y esta respuesta se acompañó de una importante pérdida de biomasa. Se concluye que el genotipo eSS se desempeña mejor en ambientes "pobres" y que el efecto beneficioso de la restricción calórica se enmascara en animales de más edad (AU)