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This version published online on November 14, 2002
Molecular Endocrinology, doi:10.1210/me.2002-0306
A more recent version of this article appeared on February 1, 2003
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Submitted on September 4, 2002
Accepted on October 30, 2002

Glucagon-like peptides: Regulators of cell proliferation, differentiation and apoptosis

Daniel J Drucker1*

1 From the Department of Medicine, Toronto General Hospital, University Health Network, Banting and Best Diabetes Centre, University of Toronto, Toronto, Canada M5G2C4

* To whom correspondence should be addressed. E-mail: d.drucker{at}utoronto.ca.

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 injury. Both GLP-1 and GLP-2 exert anti-apoptotic 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 GPCR 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.
Key words: Apoptosis • regeneration • peptide therapeutics • diabetes • intestinal injury • G protein coupled receptors




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