Abstract

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.

Highlights

  • ESS is a rat model of type 2 diabetes characterized by fasting hyperglycemia, glucose intolerance, hyperinsulinemia and early hypertriglyceridemia

  • The eSS rat is a spontaneously diabetic model obtained in Rosario, Argentina, by genetic manipulation; the generation has been described in detail by Martinez et al [5]. eSS rats develop a mild type 2-diabetes not related to obesity with higher expression in males [5,6]

  • Normoglycemic in fasting state [5,7]. These results point out that in eSS rats fasting hyperglycemia would be a later stage in the sequence of events from insulin resistance to overt diabetes, whilst the insulin resistance affects the lipid metabolism beforehand

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Summary

Introduction

ESS is a rat model of type 2 diabetes characterized by fasting hyperglycemia, glucose intolerance, hyperinsulinemia and early hypertriglyceridemia. Diabetes mellitus extensively alters lipid metabolism and, in turn, dyslipidemia appears to play an integral role in the development of impaired insulin secretion [1]. ESS rats develop a mild type 2-diabetes not related to obesity with higher expression in males [5,6]. Until 12 months of age, progressive rising values of fasting hyperglycemia and glucose intolerance are accompanied by Taking advantage of the naturally slow progress of the metabolic derangement in this model and the consequent long-life-span of the eSS rats, we have performed the study of lipid metabolic alterations in 12-month-old rats analyzing their role in this spontaneous type 2 diabetic syndrome and its complications

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