Myocardial salvaging effects and mechanisms of dipeptidyl peptidase-IV inhibitor Vildagliptin in experimental diabetes

Background: Morbidity, mortality and re-infarction rate are higher following myocardial infarction in diabetics than nondiabetic subjects.Recently, glucagon-like peptide (GLP)-1 was shown to have cardioprotective effects, but treatment with GLP-1 is limited by its short half-life.It is rapidly degraded by the enzyme dipeptidyl peptidase-IV (DPP-IV).We hypothesized that DPP-IV inhibitor Vildagliptin will increase levels of GLP-1 and may confer cardioprotective effects in setting of diabetes beyond its effect on glycemia.Methods: Diabetes was induced with single dose of Streptozotocin (STZ): 45mg/kg ip and myocardial infarction was produced by administering isoproterenol (ISP): (85mg/kg, sc) to rats 24 and 48 h prior to sacrification (5 th week).After the confirmation of diabetes on 7 th day (Glucose≥200mg/dl), Vildagliptin (10 mg/kg) was administered and various parameters like anti-diabetic (Glucose, HbA1c), cardioprotective (CPK-MB, hs-CRP), hypolipidemic (lipid profile, artherogenic potential), antioxidant (MDA) safety {pancreatic function (lipase), liver function (SGPT), kidney function (Creatinine)} and histopathological indices of injury were evaluated in experimental groups.Results: Vildagliptin (10 mg/kg) treatment demonstrated significant antidiabetic as well as myocardial salvaging effects as indicated by restoration of blood glucose, HbA1c and CPK-MB levels compared to Diabetic-ISP Control group.In addition, Vildagliptin favorably modulated the lipid parameters (TC, TG, HDL-C, LDL-C), artherogenic index, lipid peroxidation (MDA), Subsequent to ISP challenge, histopathological assessment of heart, pancreas and biochemical indices of injury confirmed the cardioprotective effects of Vildagliptin in setting of diabetes. Conclusion:The present study concluded that Vildagliptin treatment demonstrated myocardial salvaging effects in type II diabetic rats challenged with experimental Myocardial infarction.