Pancreatic -Cells Leads to Increased -Cell Mass and

naling pathways in pancreatic -cells have been implicated in the development of diabetes, in part through the regulation of -cell mass in vivo. Studies in vitro have shown that the protein Ras homolog enriched in brain (Rheb) plays a key role as a positive upstream regulator of the mammalian target of rapamycin complex 1 (mTORC1) pathway in integrating inputs from nutrients and growth factors for cell growth. Our objective was to investigate the role of the mTORC1 pathway in the regulation of -cell mass in vivo. RESEARCH DESIGN AND METHODS—We generated trans-genic mice that overexpress Rheb in -cells. We examined the activation of the mTORC1 pathway and its effects on -cell mass, on glucose metabolism, and on protection against hyperglycemia. RESULTS—Immunoblots of islet extracts revealed that the phosphorylation levels of ribosomal protein S6 and eukaryotic initiation factor 4E binding protein 1, downstream effectors fo