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Glucagon-like peptides: regulators of cell proliferation, differentiation, and apoptosis Drucker DJMol Endocrinol 2003[Feb]; 17 (2): 161-71Peptide 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.|Animals[MESH]|Apoptosis/drug effects/*physiology[MESH]|Cell Differentiation/drug effects/*physiology[MESH]|Cell Division/drug effects/physiology[MESH]|Exocrine Glands/cytology/drug effects[MESH]|Glucagon-Like Peptide 1[MESH]|Glucagon-Like Peptide 2[MESH]|Glucagon-Like Peptide-1 Receptor[MESH]|Glucagon/pharmacology/*physiology[MESH]|Humans[MESH]|Intestines/cytology/drug effects[MESH]|Islets of Langerhans/cytology/drug effects[MESH]|Peptide Fragments/pharmacology/*physiology[MESH]|Peptide Hormones/metabolism[MESH]|Peptides/pharmacology/*physiology[MESH]|Protein Precursors/pharmacology/*physiology[MESH]|Receptors, Glucagon/physiology[MESH]|Signal Transduction[MESH] |
