Gastrointestinal hormones and the regulation of ?-cell mass
Type 2 diabetes occurs due to a relative deficit in ?-cell mass or function. Glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), cholecystokinin (CCK), and gastrin are gastrointestinal hormones that are secreted in response to nutrient intake, regulating digestion, insulin secretion, satiety, and ?-cell mass. In this review, we focus upon ?-cell mass regulation. ?-cell mass expands through ?-cell proliferation and islet neogenesis; ?-cell mass is lost via apoptosis. GLP-1 and GIP are well-studied gastrointestinal hormones and influence ?-cell proliferation, apoptosis, and islet neogenesis. CCK regulates ?-cell apoptosis and mitogenesis, and gastrin stimulates islet neogenesis. GLP-1 and GIP bind to G protein-coupled receptors and regulate ?-cell mass via multiple signaling pathways. The protein kinase A pathway is central to this process because it directly regulates proliferative and anti-apoptotic genes and transactivates several signaling cascades, including Akt and mitogen-activated protein kinases. However, the signaling pathways downstream of G protein-coupled CCK receptors that influence ?-cell mass remain unidentified. Gastrointestinal hormones integrate nutrient signals from the gut to the ?-cell, regulating insulin secretion and ?-cell mass adaptation.
?-cell glp-1 gip cck gastrin islet protein kinase b/akt