Effect of Irbesartan on Glucose Tolerance in a Type 2 Diabetes Mellitus Mouse Model

Abstract

Background: 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 and ARBs are recommended in patients with comorbid diabetes and hypertension. However, the effect of irbesartan on insulin resistance and glucose tolerance is inconclusive and contradicting.

Objectives: To evaluate the effect of irbesartan on blood glucose levels and glucose tolerance in diabetic and non-diabetic mice.

Materials and methods: Diabetes was induced in 18 obese BALB/c mice fed on high fat diet using alloxan monohydrate 150mg/kg via the intra-peritoneal route. Non-diabetic mice were assigned to three treatment groups (n=6/group) and each group received either of the following treatments: 20mg/kg irbesartan or 75mg/kg irbesartan or vehicle. Diabetic mice were also divided into three groups and each group received one of the three treatments mentioned above. Drug administration was done daily via oral gavage for 14 days. Blood glucose levels were measured on day 1 (baseline values), day 8, and day 13 of treatment.  An oral glucose tolerance test was carried out on day 14 after administration of 50% dextrose at the dose of 1g/kg body weight. Blood glucose levels at 15, 30, 60 and 120 minutes were measured during the oral glucose tolerance test.

Results: Irbesartan at the dose of 20mg/kg (-39.44% ±8.96, p=0.0177) and 75mg/kg (-40.07% ±6.27, p=0.0111) significantly lowered blood glucose levels in diabetic mice. However, irbesartan 20mg/kg (-14.87% ±10.13, p>0.9999) and 75mg/kg (-9.07%±3.77, p>0.9999) did not significantly change blood glucose levels in non-diabetic mice. In non-diabetic mice there was only a modest difference in AUC in the irbesartan20mg/kg (AUC=28.73mmol/Lmin, p=0.6435), 75mg/kg (AUC=26.66mmol/Lmin, p>0.9999) compared to the non-diabetic control (AUC=26.63 mmol/Lmins). Although there was a slight improvement in glucose tolerance in diabetic mice, irbesartan 20mg/kg (AUC=55.35mmol/Lmin, p>0.9999) and 75mg/kg (AUC=45.54mmol/Lmin, p=0.1737) had no significant effect on glucose tolerance compared to the diabetic control group (AUC=63.53mmol/Lmin).

Conclusion: At standard treatment doses, irbesartan had a significant hypoglycaemic effect without significantly improving glucose tolerance in diabetic mice.

Key words: Irbesartan, glycemic effects, glucose tolerance, Type 2 diabetes, mouse model