Atorvastatin targets islet mTOR signaling via regulating small G proteins to reduce functional β-cell mass

Statins, the cholesterol lowering agents, can increase diabetes incidence and impair glucose tolerance via its detrimental effects on non-hepatic tissues, such as pancreatic islet, but underlying mechanism has not been clarified. In atorvastatin-treated high fat diet mice, we found reduced pancreatic β-cell size, β-cell mass, mature insulin granules and reduced insulin secretion along with the deteriorated glucose tolerance. Transcriptome profiling of primary pancreatic islets showed inhibitory effects of atorvastatin on expression of genes encoding key pancreatic transcription factors, mTOR signaling pathway and small G proteins (sGPs).