ROLE OF THIAZOLIDINEDIONES (TZDs) AND GLUCAGON-LIKE PEPTIDE-1 (GLP-1) AGONISTS AND ANTAGONOSTS IN TYPE-II DIABETES MELLITUS ON ADULT MALE ALBINO RATS

Abstract

Background: The rising incidence of insulin resistance to epidemic proportions has closely paralleled the surge in the prevalence of diabetes and outpaced therapeutic advances in diabetes prevention and treatment. Thiazolidinediones and glucagon-like peptide-1 agonists are insulinotropic peptides and are being evaluated for the regulation of lipid profile in diabetes mellitus (DM). Thiazolidinedione and glucagon-like peptide-1 antagonists have anti- insulinotropic effects. Objectives: Evaluating the possible effects of thiazolidinediones and glucagon-like peptide-1 agonists, and their antagonists in lipoststic function in diabetic male albino rats. Materials and Methods: Seventy adult male albino rats were divided into seven equal groups: Group I served as a normal control group, group II was diabetic control, group III was diabetic group treated with thiazolidinedione agonist (pioglitazone), group IV was diabetic group treated with glucagon-like peptide-1 agonists (exendin-4), and group V was diabetic group treated with both pioglitazone and exendin-4, group VI was diabetic group treated with thiazolidinedione antagonist [Bisphenol A diglycidyl Ether (BADGE)], and group VII was diabetic group treated with glucagon-like peptide-1 antagonist (Exendin- 9-39). At the end of the experimental period, blood samples were collected for measuring of fasting blood glucose, insulin level, total cholesterol, triglycerides (TG), low density lipoproteins (LDL), high density lipoproteins (HDL), aspartate transaminase (AST), and alanine transaminase (ALT). Body weights at the beginning and at the end of the study were determined. Results: Alloxan-induced diabetes mellitus was associated with significant higher levels of serum blood glucose, total cholesterol, TG and LDL-C, AST, and ALT, with significant lower levels of insulin, and HDL-C as compared to the control normal group. Pioglitazone, exendin-4 or both showed significant lower levels of blood glucose, total cholesterol, TG, LDL-C, AST, and ALT, and significant higher levels of insulin and HDL-C as compared with the control diabetic rats. BADGE and exendin-9-39 revealed significant higher levels of serum blood glucose, total cholesterol, TG, LDL-C, AST, and ALT, and significant lower levels of insulin and HDL-C as compared with the control normal group. As regards the differences between pioglitazone (group III) with exendine-4 group (group IV), the obtained data showed insignificant changes in all parameters. There were insignificant changes also between groups VI and VII in all parameters. Conclusion: Thiazolidinediones and glucagon- like peptide-1 agonists therapy has a marked effect on improvement of blood glucose, lipid profile and liver enzymes, while their antagonists blocked insulin secretion and impaired liver enzymes.