title: Minireview: Glucagon-like peptides regulate cell proliferation and apoptosis in the pancreas, gut, and central nervous system.
abstract: Gut peptides exert diverse effects regulating satiety, gastrointestinal motility and acid secretion, epithelial integrity, and both nutrient absorption and disposal. These actions are initiated by activation of specific G protein-coupled receptors and may be mediated by direct or indirect effects on target cells. More recent evidence demonstrates that gut peptides, exemplified by glucagon-like peptides-1 and 2 (GLP-1 and GLP-2), directly regulate signaling pathways coupled to cell proliferation and apoptosis. GLP-1 receptor activation enhances beta-cell proliferation and promotes islet neogenesis via activation of pdx-1 expression. The proliferative effects of GLP-1 appear to involve multiple intracellular pathways, including stimulation of Akt, activation of protein kinase Czeta, and transactivation of the epidermal growth factor receptor through the c-src kinase. GLP-1 receptor activation also promotes cell survival in beta-cells and neurons via increased levels of cAMP leading to cAMP response element binding protein activation, enhanced insulin receptor substrate-2 activity and, ultimately, activation of Akt. These actions of GLP-1 are reflected by expansion of beta-cell mass and enhanced resistance to beta-cell injury in experimental models of diabetes in vivo. GLP-2 also promotes intestinal cell proliferation and confers resistance to cellular injury in a variety of cell types. Administration of GLP-2 to animals with experimental intestinal injury promotes regeneration of the gastrointestinal epithelial mucosa and confers resistance to apoptosis in an indirect manner via yet-to-be identified GLP-2 receptor-dependent regulators of mucosal growth and cell survival. These proliferative and antiapoptotic actions of GLP-1 and GLP-2 may contribute to protective and regenerative actions of these peptides in human subjects with diabetes and intestinal disorders, respectively.
authors.affiliation: Room 3366, Medical Science Building, University of Toronto, 1 King's College Circle, Toronto, Ontario, Canada M5S 1A8. p.brubaker@utoronto.ca
authors.forename: P L
authors.initials: PL
authors.lastname: Brubaker
authors.forename: D J
authors.initials: DJ
authors.lastname: Drucker
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002455:Cell Division / Q000502:physiology; D002490:Central Nervous System / Q000502:physiology*; D005934:Glucagon / Q000502:physiology*; D052216:Glucagon-Like Peptide 1; D053767:Glucagon-Like Peptide 2; D007422:Intestines / Q000166:cytology* / Q000502:physiology; D010179:Pancreas / Q000166:cytology* / Q000502:physiology; D010446:Peptide Fragments / Q000502:physiology*; D010455:Peptides / Q000502:physiology*; D011498:Protein Precursors / Q000502:physiology*
chemical_list: D053767:Glucagon-Like Peptide 2; D010446:Peptide Fragments; D010455:Peptides; D011498:Protein Precursors; D052216:Glucagon-Like Peptide 1; D005934:Glucagon