Effects of pioglitazone and metformin on carbohydrate metabolism in experimental models of glucose intolerance

The aim of the study was to compare the effects of pioglitazone and metformin on carbohydrate metabolism in diabetic and insulin resistant rats. Male albino rats were randomized into seven groups. The first, control group received high carbohydrate diet. The second, third and fourth groups were fed high fat diets for 6 weeks and either left untreated, or given pioglitazone (2.7 mg/kg/day) or metformin (180 mg/kg/day) in the last 3 weeks. The 5 th , 6 th , and 7 th groups were made diabetic by single intraperitoneal injection of streptozotocin (STZ, 50 mg/kg) on day 15 of the 6-week high fat regimen. They were either left untreated, or given pioglitazone or metformin in the last 3 weeks. High fat diet induced insulin resistance evidenced by increased serum glucose, associated with increase in liver glucose-6-phosphatase and decrease in liver glucose6-phosphate dehydrogenase and glucokinase activities. No significant difference was observed between rats treated with either pioglitazone or metformin. Both treatments showed significant increase in glucose-6-phosphate dehydrogenase activity by ~20 %, decrease in glucose-6-phosphatase activity by ~25 %, and decreases in liver and kidney glycogen. In diabetic rats, both pioglitazone and metformin decreased elevated serum glucose by ~30 %. Only metformin caused more than 2-fold increase in hepatic glycogen content, and normalized glucose-6-phosphatase activity. Only pioglitazone normalized elevated renal glycogen content and increased glucose-6-phosphate dehydrogenase activity. In conclusion pioglitazone and metformin had comparable effects on estimates of carbohydrate metabolism and insulin sensitivity in insulin resistant rats, but different effects in diabetic rats.