Department of Medicine, Banting and Best Diabetes Centre, Toronto
General Hospital, University of Toronto, Toronto, Ontario, Canada M5G
2C4
Address correspondence and requests for reprints to: Dr. D. J. Drucker, Toronto General Hospital, 101 College Street CCRW3-845, Toronto, Ontario, Canada M5G 2C4. E-mail: d.drucker{at}utoronto.ca
Glucagon-like peptide 2 (GLP-2) is a 33 amino acid peptide-encoded
carboxyterminalto the sequence of GLP-1 in the
proglucagon gene. Both GLP-1and GLP-2 are secreted from
gut endocrine cells and promotenutrient absorption through distinct
mechanisms of action. GLP-2regulates gastric motility, gastric acid
secretion, intestinalhexose transport, and increases the barrier
function of thegut epithelium. GLP-2 significantly enhances the
surface areaof the mucosal epithelium via stimulation of crypt cell
proliferationand inhibition of apoptosis in the enterocyte and crypt
compartments.The cytoprotective and reparative effects of GLP-2 are
evidentin rodent models of experimental intestinal injury. GLP-2
reducesmortality and decreases mucosal injury, cytokine expression,
andbacterial septicemia in the setting of small and large bowel
inflammation.GLP-2 also enhances nutrient absorption and gut
adaptation inrodents or humans with short bowel syndrome. The actions
ofGLP-2 are transduced by the GLP-2 receptor, a G protein-coupled
receptorexpressed in gut endocrine cells of the stomach, small bowel,
andcolon. Activation of GLP-2 receptor signaling in heterologouscells
promotes resistance to apoptotic injury in vitro. The
cytoprotective,reparative, and energy-retentive properties of GLP-2
suggeststhat GLP-2 may potentially be useful for the treatment of
humandisorders characterized by injury and/or dysfunction of the
intestinalmucosal epithelium.
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