Role of Dipeptidyl Peptidase-4 Inhibitor in the Control of Glycemic State in Type I and Type II Diabetes Mellitus in Rats: A Comparative Study

Abstract

AbstractBackground: Incretin hormones; glucose-dependent in-sulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) have attracted considerable scientific and clinical interest due largely to their insulin-releasing and glucose-lowering properties. Dipeptidyl peptidase-4 (DPP-4) is the enzyme responsible for cleavage and inactivation of GIP and GLP-1.Aim of Study: The present investigation was assigned to study and compare the effect of DPP-4 inhibitor (vildagliptin) on glycemic state in type I and type II diabetes mellitus in rats.Material and Methods: Fifty male albino rats of local strain were used. Rats were divided into three groups: Non-diabetic (10 rats); type I diabetic (non-treated, 10 rats and Vildagliptin-treated, 10 rats); type II diabetic (non-treated group, 10 rats and Vildagliptin-treated, 10 rats). Type I diabetes was induced by a single intraperitoneal injection (60mg/kg) of STZ dissolved in 0.2ml citrate buffer in adult 6 weeks old rats. 48h later fasting blood samples were taken from rat tail and rats with fasting blood glucose levels greater than 250mg/dl were considered diabetic type I. They were left for 30 days before assessment. Type II diabetes was induced by a single intra-peritoneal injection (90mg/kg) of STZ to a group of 2 days old pups. 6 weeks later, fasting blood samples were taken from rat tail and rats with fasting blood glucose level ³160mg/dl were considered as diabetic type II, they were left for 30 days before assessment. In both treated groups rats were treated daily with Vildagliptin (5mg/kg) by oral gavage for 30 days. At the end of the experiment, retro-orbital fasting blood sample was taken for measurement of serum glucose, serum insulin, glycated hemoglobin (HbA1c), plasma GLP-1 levels, lipid profile, malondialdehyde and total antioxidant capacity. Homeostasis model assessment of insulin resistance (HOMA-IR) index was calculated.Results: Serum glucose, blood HbA1c, serum cholesterol, triglycerides (TG), low density lipoprotein-cholesterol (LDL-cholesterol) and malondialdehyde (MDA) were significantly higher in type I and type II diabetic non-treated groups when compared to corresponding values in non- diabetic group. All the previous parameters were significantly lower in diabetic type I and type II vildagliptin-treated groups when compared to corresponding values in non-treated groups and the same parameters were significantly lower in type II Vildagliptin-treated group when compared to corresponding values in type I vildagliptin-treated group. Serum insulin, high density lipoproteins (HDL-cholesterol) and total antioxidant capacity (TAC) in type I and type II diabetic non-treated groups were significantly lower when compared to corresponding values in non-diabetic group, while all the previous parameters were significantly higher in type I and type II Vildagliptin-treated groups when compared to corresponding values in type I and type II diabetic non-treated groups. The same parameters were significantly higher in type II Vildagliptin-treated group when compared to corresponding values in type I vildagliptin treated group. There was insignificant change in HOMA-IR and plasma GLP-1 level in type I diabetic (both non-treated and Vildagliptin-treated) groups when compared to corresponding values in non-diabetic group; on the other hand HOMA-IR was significantly higher while plasma GLP-1 level was sig-nificantly lower in type II diabetic non- treated group when compared to corresponding values in non-diabetic group. In type II diabetic Vildagliptin-treated group HOMA-IR was significantly lower while plasma GLP-1 level was significantly higher when compared to corresponding values in non-treated group. Upon comparing type I and type II non-treated groups; serum glucose, HbA1c and plasma GLP-1 were significantly higher while serum insulin and HOMA-IR were significantly lower in type I non-treated group when compared to corre-sponding values in type II non-treated group. On the other hand there was insignificant difference in all other parameters between the two groups.Conclusion: Vildagliptin treatment is a good choice for type II diabetes treatment and has beneficial effects in type I diabetes.