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Pleiotropic effects of metformin in managing type 2 diabetes and metabolic syndrome: evidences from experimental mouse model

Christina Gertrude Yap, Rakesh Naidu, Kim Dae Jin, Srinivasa Rao Sirasanagandla, Narendra Pamidi

Background: Metformin is the common first-line medication for treating type 2 diabetes. Besides its anti-hyperglycemic property, various studies have isolatedly shown its effectiveness in reducing body weight and ameliorated components of metabolic syndrome. However, it has not been evidently shown weather metformin is effective as a dual treatment in cases of diet induced obesity and diabetes. We optimized a mouse model for diet induced obesity and diabetes for evaluating dual effectiveness of metformin in treating obesity and diabetes and simultaneously demonstrated histological changes in obese and diabetic kidney and heart tissues and the cellular-protective effects of metformin on these tissues.

Methods: BULB/c mice were fed with normal, high fat or high sucrose diets for 26 w. All groups were treated with metformin from w 16 to 26. Blood samples were collected and body weights recorded on d 1 and forth nightly till w 26 when all animals were sacrificed. Hearts and kidneys were dissected and prepared for historical observation. Blood samples were processed accordingly for quantitating blood glucose, ROS and ROS defense (d 1 and d 182).

Results: HFD and HSS feeds successfully created diet induced by obesity and diabetes by w 15. Metformin significantly lowered the average body weight of obese group (p<0.05) as well as the average blood glucose levels of the diabetes group (p<0.005) relative to the respective control groups. Histological studies showed no morphological cellular changes in heart and kidney tissues of obese and diabetic mice relative to respective controls (untreated). Cell shrinkage/‘sick cells” were seen in the untreated obese and diabetic mice. ROS levels in the metformin treated mice remained normal relative to the untreated control groups (p<0.05).

Conclusions: We have optimized a reliable mouse model for obesity and diabetes. Metformin is effective for controlling diet induced obesity and diabetes. Metformin also showed protection against obesity and hyperglycemia related cell morphological changes.