Effects of metformin on compensatory pancreatic ß-cell hyperplasia in mice fed a high-fat diet.

ABSTRACT

Metformin has been widely used for the treatment of type 2 diabetes. However, the effect of metformin on pancreatic ß-cells remains controversial. In this study, we investigated the impacts of treatment with metformin on pancreatic ß-cells in a mouse model fed a high-fat diet (HFD), which triggers adaptive ß-cell replication. An 8-wk treatment with metformin improved insulin resistance and suppressed the compensatory ß-cell hyperplasia induced by HFD-feeding. In contrast, the increment in ß-cell mass arising from 60 wk of HFD feeding was similar in mice treated with and those treated without metformin. Interestingly, metformin suppressed ß-cell proliferation induced by 1 wk of HFD feeding without any changes in insulin resistance. Metformin directly suppressed glucose-induced ß-cell proliferation in islets and INS-1 cells in accordance with a reduction in mammalian target of rapamycin phosphorylation. Taken together, metformin suppressed HFD-induced ß-cell proliferation independent of the improvement of insulin resistance, partly via direct actions.