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.

Both diabetes mellitus type 1 and diabetes mellitus type 2 are widespread diseases that alter carbohydrate and lipid metabolism. e Stilmann-Salgado (eSS) rats are experimental animals that spontaneously evolve to a state similar to that of young people affected by non-insulin-dependent diabetes mellitus (NIDDM; type 2). Using 6-mon-old eSS rats that, according to the literature [Martinez, S.M., Tarrés, M.C., Montenegro, S., Milo, R., Picena, J.C., Figueroa, N., and Rabasa, S.R. (1988) Spontaneous Diabetes in eSS Rats, Acta Diabetol. Lat. 25, 303-313], had already developed insulin resistance, we investigated the changes evoked on delta9, delta6, and delta5 liver desaturases. The abundance of mRNA and enzymatic activities were measured, as well as the FA composition of liver microsomal lipids. Compared to control rats, the mRNA content and activity of SCD-1 (stearoyl CoA-desaturase, isoform of the delta9 desaturase) were significantly higher, whereas the mRNA and activities of delta6 and delta5 desaturases were not significantly modified. Correspondingly, the proportion of 18:1n-9 and the ratios of 18:1n-9/18:0 and 16:1/16:0 in lipids were significantly increased, whereas the proportion of 20:4n-6 was unaltered. These effects were found while glycemia was constant or increased. The results are completely opposite those described in insulin-dependent diabetes mellitus (type 1), in which a depression of all the desaturases is found. They suggest that in eSS rats, the activities of the desaturases were not modified by an insulin-resistance effect. Moreover, we suggest that the enhancement of SCD-1 activity might be considered as another typical sign of the NIDDM syndrome, because it has also been found in other animal models of NIDDM, for example, the ones evoked by the sucrose-rich diet and in the Zucker rat.

BackgroundeSS is a rat model of type 2 diabetes characterized by fasting hyperglycemia, glucose intolerance, hyperinsulinemia and early hypertriglyceridemia. Diabetic symptoms worsen during the second year of life as insulin release decreases. In 12-month-old males a diffuse hepatic steatosis was detected. We report the disturbances of lipid metabolism of the model with regard to the diabetic syndrome.MethodsThe study was conducted in eight 12-month-old eSS male rats and seven age/weight matched eumetabolic Wistar rats fed with a complete commercial diet al libitum. Fasting plasmatic glucose, insulin, triglycerides, total cholesterol, low-density and high-density lipoprotein, and nonesterified fatty acids levels were measured. Very low density and intermediate-density lipoproteins were analyzed and hepatic lipase activity was determined.ResultseSS rats developed hyperglycemia and hyperinsulinemia, indicating insulin resistance. Compared with controls, diabetic rats exhibited high plasmatic levels of NEFA, triglycerides (TG), total cholesterol (Chol) and LDL-Chol while high-density lipoprotein (HDL) cholesterol values were reduced. eSS rats also displayed TG-rich VLDL and IDL particles without changes in hepatic lipase activity.ConclusionThe nonobese eSS rats develop a syndrome characterized by glucose and lipid disorders and hepatic steatosis that may provide new opportunities for studying the pathogenesis of human type 2 diabetes.

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