Histopathological Alteration in STZ-Nicotinamide Diabetic Rats, a Complication of Diabetes or a Toxicity of STZ?

Background: Type 2 diabetes mellitus (T2DM) previously known as non-insulin dependent diabetes mellitus is the most common type of diabetes mellitus. The rapid increasing prevalence, high morbidity and mortality of the disease must be encountered by an increase in scientific research. Animal models are very important in the preclinical studies to validate the use of new drugs. Streptozotocin nicotinamide (STZ-NA) is used to induce T2DM in animals. Aim: The aim of this study was to assess STZ-NA as a model of T2DM and to investigate the causative factors that lead to hepatic histopathological changes. Methodology: Twenty-five male Wistar rats were divided into four groups. One normal non-diabetic control group (NNC) (n = 6), two diabetic groups subdivided into non-treated diabetic group (NTD) (n = 6) and metformin treated diabetic group (MTD) (n = 7) and the fourth group was composed of rats failed to develop diabetes [failed induction group (FIG)] (n = 6). Diabetes was induced by a single intraperitoneal injection of STZ (65 mg/kg-bw) 15 min after intraperitoneal administration of nicotinamide (120 mg/kgbw). Induction of diabetes was confirmed after 72 hours by fasting blood glucose (FBG) ≥ 250 mg/dl. 8 weeks after induction, oral glucose tolerance test was performed; blood samples were taken for analysis of lipid profile, urea, creatinine and hepatic enzymes; samples from the liver were prepared for histopathological study and samples from the skeletal muscles were taken for determination of insulin receptor content by Elisa. Results: Metformin improved glucose intolerance. Serum high density lipoprotein cholesterol (HDL-C) was significantly reduced in the NTD group compared with the NNC group (P value 0.006) whereas no significant difference in low density lipoprotein cholesterol and triglycerides detected. Skeletal muscle insulin receptor was reduced in both diabetic groups yet, reduction was significant in MTD group compared with NTD group [P values were (0.01) and (0.06) in the MTD and NTD respectively]. Hepatic enzymes, urea and creatinine were within normal range. Histopathological study revealed hepatic histopathological alterations which were more obvious in NTD compared with MTD and FIG. Conclusion: Our study showed that STZ-NA is a good model for T2DM regarding hyperglycemia, response to metformin, dyslipidemia and the histopathological changes. In addition, it emphasized that hepatic hydropic degeneration of the hepatocytes was a consequence of diabetes rather than STZ.