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GLUT2 and the incretin receptors are involved in glucose-induced incretin secretion

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  • Patrice D Cani
  • Holst, Jens Juul
  • Daniel J Drucker
  • Nathalie M Delzenne
  • Bernard Thorens
  • Rémy Burcelin
  • Claude Knauf

Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are incretins secreted in response to oral glucose ingestion by intestinal L and K cells, respectively. The molecular mechanisms responsible for intestinal cell glucose sensing are unknown but could be related to those described for beta-cells, brain and hepatoportal sensors. We determined the role of GLUT2, GLP-1 or GIP receptors in glucose-induced incretins secretion, in the corresponding knockout mice. GLP-1 secretion was reduced in all mutant mice, while GIP secretion did not require GLUT2. Intestinal GLP-1 content was reduced only in GIP and GLUT2 receptors knockout mice suggesting that this impairment could contribute to the phenotype. Intestinal GIP content was similar in all mice studied. Furthermore, the impaired incretins secretion was associated with a reduced glucose-stimulated insulin secretion and an impaired glucose tolerance in all mice. In conclusion, both incretins secretion depends on mechanisms involving their own receptors and GLP-1 further requires GLUT2.

OriginalsprogEngelsk
TidsskriftMolecular and Cellular Endocrinology
Vol/bind276
Udgave nummer1-2
Sider (fra-til)18-23
Antal sider6
ISSN0303-7207
DOI
StatusUdgivet - 30 sep. 2007

ID: 132049904