Effect of irbesartan on blood glucose levels in a mice model of type 2 diabetes mellitus

Abstract

Angiotensin receptor blockers (ARBs) have been reported to affect glycaemic control in both animals and humans. A few studies have evaluated the effects of irbesartan on blood glucose levels. However, only one study evaluated the effect of irbesartan on insulin resistance and glucose tolerance. Objective: To evaluate the effect of irbesartan on blood glucose levels and glucose tolerance in diabetic and non-diabetic mice Method: A total of 48 mice were divided into 8 groups (n=6) where group 1-4were fed on standard diet and group 5-8were fed on high fat diet. Diabetes was induced in mice fed on high fat diet using alloxan monohydrate 150mg/kg via the intra-peritoneal route. Group 1, 2 and 3 were non-diabetic and received irbesartan at 20mg/kg, 50mg/kg and 75mg/kg for 13 days, respectively. Group 4 acted as the non-diabetic control and received water. After induction of diabetes, group 5, 6 and 7 received irbesartan 20mg/kg, 50mg/kg and 75mg/kg for 13 days, respectively, whilst group 8 acted as the diabetic control and received distilled water. Drug administration was done via oral gavage. Blood glucose levels were measured on selected days. Oral glucose tolerance test was carried out on day 14 after the commencing of drug dosing via administration of 1g/kg body weight to all the mice and measuring the blood glucose levels at 15, 30, 60 and 120 minutes. Results: Irbesartan at the dose of 20mg/kg and 75mg/kg significantly lowered (-39%, and 40%, respectively; p<0.05) blood glucose levels in diabetic mice. Irbesartan 20mg/kg, 50mg/kg and 75mg/kg did not significantly change blood glucose levels (-15%, -3% and 9%) in non-diabetic mice. In diabetic mice, irbesartan 20mg/kg and 75mg/kg improved glucose tolerance (Area under the curve [AUC] = 55.35mmol/Lmins and 45.54mmol/Lmins, respectively). However, the improvements were not statistically significant compared to the diabetic control group (AUC=63.53mmol/Lmins; p<0.05). Unlike in the diabetic mice, all the doses of irbesartan had no effect on glucose tolerance in non-diabetic mice (p<0.05) Conclusion: Low and high dose irbesartan had significant hypoglycaemic effects and improved glucose tolerance in diabetic mice. However, all doses of irbesartan had no significant effects on blood glucose levels and glucose tolerance in non-diabetic mice.