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Symposium: Glucagon-Like Peptide 2: Function and Clinical Applications

Dual Regulation of Cell Proliferation and Survival via Activation of Glucagon-Like Peptide-2 Receptor Signaling^1,2

Jennifer L. Estall^* and Daniel J. Drucker^*,,3

Departments of ^* Laboratory Medicine and Pathobiology and Medicine, Banting and Best Diabetes Centre, Toronto General Hospital, University of Toronto, Toronto, Ontario Canada M5G 2C4

³To whom correspondence should be addressed. E-mail: d.drucker{at}utoronto.ca.

Peptide hormones regulate cell viability and tissue integrity, directly or indirectly, through activation of G-protein–coupled receptors via diverse mechanisms including stimulation of cell proliferation and inhibition of cell death. Glucagon-like peptide-2 (GLP-2) is a 33 amino acid peptide hormone released from intestinal endocrine cells following nutrient ingestion. GLP-2 stimulates intestinal crypt cell proliferation leading to expansion of the gastrointestinal mucosal epithelium. Exogenous GLP-2 administration attenuates intestinal injury in experimental models of gastrointestinal disease and improves intestinal absorption and nutritional status in human patients with intestinal failure secondary to short bowel syndrome. GLP-2 also promotes mucosal integrity via reduction of injury-associated apoptosis in the intestinal mucosa and directly reduces apoptosis in cells expressing the GLP-2 receptor in vitro. Hence, the regenerative and cytoprotective properties of GLP-2 contribute to its therapeutic potential for the treatment of patients with intestinal disease.

KEY WORDS: • glucagon-like peptide-2 • apoptosis • GPCR • intestine

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