Glucagon-like peptides: regulators of cell proliferation, differentiation, and apoptosis.
Peptide hormones are secreted from endocrine cells and neurons and exert their actions through activation of G protein-coupled receptors to regulate a diverse number of physiological systems including control of energy homeostasis, gastrointestinal motility, neuroendocrine circuits, and hormone secretion. The glucagon-like peptides, GLP-1 and GLP-2 are prototype peptide hormones released from gut endocrine cells in response to nutrient ingestion that regulate not only energy absorption and disposal, but also cell proliferation and survival. GLP-1 expands islet mass by stimulating pancreatic beta-cell proliferation and induction of islet neogenesis. GLP-1 also promotes cell differentiation, from exocrine cells or immature islet progenitors, toward a more differentiated beta-cell phenotype. GLP-2 stimulates cell proliferation in the gastrointestinal mucosa, leading to expansion of the normal mucosal epithelium, or attenuation of intestinal injury in experimental models of intestinal disease. Both GLP-1 and GLP-2 exert antiapoptotic actions in vivo, resulting in preservation of beta-cell mass and gut epithelium, respectively. Furthermore, GLP-1 and GLP-2 promote direct resistance to apoptosis in cells expressing GLP-1 or GLP-2 receptors. Moreover, an increasing number of structurally related peptide hormones and neuropeptides exert cytoprotective effects through G protein-coupled receptor activation in diverse cell types. Hence, peptide hormones, as exemplified by GLP-1 and GLP-2, may prove to be useful adjunctive tools for enhancement of cell differentiation, tissue regeneration, and cytoprotection for the treatment of human disease.
Drucker
Daniel J
DJ
Department of Medicine, Toronto General Hospital, University Health Network, Banting and Best Diabetes Centre, University of Toronto, Toronto, Canada M5G 2C4. d.drucker@utoronto.ca
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D005088:Exocrine Glands / Q000166:cytology / Q000187:drug effects; D005934:Glucagon / Q000494:pharmacology / Q000502:physiology*; D052216:Glucagon-Like Peptide 1; D053767:Glucagon-Like Peptide 2; D000067757:Glucagon-Like Peptide-1 Receptor; D006801:Humans; D007422:Intestines / Q000166:cytology / Q000187:drug effects; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects; D010446:Peptide Fragments / Q000494:pharmacology / Q000502:physiology*; D036361:Peptide Hormones / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology / Q000502:physiology*; D011498:Protein Precursors / Q000494:pharmacology / Q000502:physiology*; D018027:Receptors, Glucagon / Q000502:physiology; D015398:Signal Transduction
C000593833:GLP1R protein, human; D053767:Glucagon-Like Peptide 2; D000067757:Glucagon-Like Peptide-1 Receptor; D010446:Peptide Fragments; D036361:Peptide Hormones; D010455:Peptides; D011498:Protein Precursors; D018027:Receptors, Glucagon; D052216:Glucagon-Like Peptide 1; D005934:Glucagon