Molecular biology of gluco-incretin function

Abstract

The gluco-incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon like peptide-1 (GLP-1) are secreted by intestinal endocrine cells and have been studied for many years because of their important effect to potentiate glucose-stimulated insulin secretion. In contrast to GIP, GLP-1 retains its insulinotropic effect in type 2 diabetic patients and a long-acting agonist of this peptide is now used for the treatment of this disease. Both peptides, however, have also long-term beneficial effect on the preservation or augmentation of the pancreatic beta-cell functional mass by stimulating beta-cell differentiation from precursors, proliferation of mature beta cells, and their protection against apoptosis. Although several studies have investigated the underlying molecular mechanisms, much remains to be learned about the mode of action of these hormones on beta cells. Here we review the current knowledge on gluco-incretin biology with a specific perspective on their beta-cell action. We also discuss the role that GLP-1 has on beta cells through indirect mechanisms, in particular through the regulation of the hepatoportal vein glucose sensors. This serves as a reminder that betacell function needs to be also studied in an integrated physiological approach where the complexity of their functional regulation can be appreciated. © 2008 Springer.