COMPARATIVE EFFECTS OF LOSARTAN AND PIOGLITAZONE ON INSULIN RESISTANCE IN RATS

Background: Insulin resistance is a key feature of type 2 diabetes mellitus. Peroxisome Proliferator activated receptor – gamma (PPAR-γ) agonists are known to decrease insulin resistance. The renin angiotensin aldosterone system (RAAS) is also implicated in the development of insulin resistance; drugs acting on this system are expected to improve it. Objective of this study was to evaluate the beneficial role, of losartan in comparison with pioglitazone on insulin resistance in a type 2 diabetic rat model fed on high fat and sucrose diet. Methods: A total of 45 Sprague – Dawley rats of 5 weeks of age were randomized into three groups. All the rats were fed a high fat (HFD) and sucrose diet. Pioglitazone (PIO) and losartan (LOS) was given along with this diet to the rats in group HFD–PIO and HFD–LOS respectively, while group HFD was kept as control. Body weight and fasting blood glucose levels were determined weekly. At the end of 12 weeks, insulin tolerance test (ITT) was performed in all groups. Serum insulin and C-reactive protein (CRP) levels were also determined. Markers of insulin sensitivity, Homeostatic Model assessment of insulin resistance (HOMA–IR) and quantitative insulin sensitivity check index (QUICKI) were calculated. Results: At the end of study period body weight, fasting blood glucose, serum insulin, C-reactive protein and HOMA–IR had significantly lower values and QUICKI had a significantly higher value in both experimental groups as compared to group HFD. Insulin tolerance test gave significantly lower blood glucose levels at all reading times in both experimental groups as compared to group HFD. Difference between group HFD–PIO and HFD–LOS was statistically insignificant for all parameters. Relationship between CRP and HOMA–IR was positive and relationship between CRP and QUICKI was negative. Conclusion: Losartan is as effective in improving insulin resistance as pioglitazone. This effect might be mediated through an anti-inflammatory mechanism.