EFFECTS OF C -PEPTIDE AND GLUCAGON-LIKE PEPTIDE-1 ON DIABETIC MALE ALBINO RATS WITH AND WITHOUT ANTIOXIDANTS

Abstract

Background: Diabetes mellitus is a major health problem with long-term complications responsible for its mortality and morbidity. Administration of C-peptide improves nervous and renal functions in diabetic patients and animals. Glucagon like peptide-1 is secreted in response to meal. It is able to increase the disposal of glucose under hyperglycemic conditions independent of its effect on insulin or glucagon. An interesting analog is exendin-4. Objective: Determination of the effects of C-peptide and glucagon-like peptide-1 analogue exendin-4 with and without antioxidants on blood and plasma levels of glucose, insulin, glucagon, lipid profile and malondialdehyde (MDA) in diabetic model of adult male albino rats. Material and Methods: Seventy adult male albino rats of local strain weighed 150-180 g were used in this study. They were divided into seven equal groups: Control group (C): Rats received saline i.p. daily for 4 weeks, Diabetes group (D1): After overnight fasting, rats received a single subcutaneous injection of alloxan monohydrate with glucose by gastric intubation to avoid fatal hypoglycemia, Diabetes with C-peptide (D2) were given alloxan and C-peptide by intraperitoneal injection for 4 weeks, Diabetes with exendin-4 (D3) were given alloxan and glucagon-like peptide -1 (GLP-1) analog exendin-4 i.p. for 4 weeks, Diabetes with C–peptide and exendin-4 (D4) were given combined intraperitoneal injection of C-peptide and exendin-4 with alloxan for 4 weeks, Diabetes with antioxidants (vitamins C & E) (D5) received alloxan, vitamin C and vitamin E by gastric intubation for 4 weeks, Diabetes with C–peptide, exendin-4 and antioxidants (vitamins C & E) (D6) received combined C-peptide, exendin-4 and vitamins C and E in by gastric intubation with alloxan for 4 weeks. Blood samples were taken from all groups. Blood glucose, plasma insulin, plasma glucagon, plasma lipid profile, and plasma level of malondialdehyde (MDA) with their relationships to C–peptide and exendin-4 (D4) treatment with and without antioxidants (vitamins C & E) supplementation were investigated. Results: Treatment of diabetic rats by C-peptide and exendin-4 caused significant reduction in total cholesterol, triglycerides, LDL, MDA and glucose with elevated insulin and HDL. Treatment of diabetic rats by C-peptide and exendin-4 with antioxidants (vitamins C & E) showed reduction of glucose, cholesterol, LDL and triglycerides with significantly elevated insulin in comparison to diabetic group. Conclusion: Adding C–peptide to exendin-4 caused significant reduction in total triglycerides, cholesterol, and more reduction of LDL than exendin-4 group. Vitamins C & E improved serum lipid profile and level of MDA as an oxidative stress indicator.