GLUT2 and the incretin receptors are involved in glucose-induced incretin secretion.
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.
Institut de Médecine Moléculaire de Rangueil, I(2)MR, IFR31, CHU Rangueil, BP 84225, 31432 Toulouse cedex 4, France.
Patrice D
PD
Cani
Jens J
JJ
Holst
Daniel J
DJ
Drucker
Nathalie M
NM
Delzenne
Bernard
B
Thorens
Rémy
R
Burcelin
Claude
C
Knauf
D000818:Animals; D005749:Gastric Inhibitory Polypeptide / Q000378:metabolism*; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism*; D000067757:Glucagon-Like Peptide-1 Receptor; D005947:Glucose / Q000494:pharmacology*; D018149:Glucose Intolerance; D005951:Glucose Tolerance Test; D051273:Glucose Transporter Type 2 / Q000172:deficiency / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D011168:Portal System / Q000187:drug effects / Q000378:metabolism; D011964:Receptors, Gastrointestinal Hormone / Q000172:deficiency / Q000378:metabolism*; D018027:Receptors, Glucagon / Q000172:deficiency / Q000378:metabolism*
C000593834:Glp1r protein, mouse; D000067757:Glucagon-Like Peptide-1 Receptor; D051273:Glucose Transporter Type 2; D011964:Receptors, Gastrointestinal Hormone; D018027:Receptors, Glucagon; D005749:Gastric Inhibitory Polypeptide; D052216:Glucagon-Like Peptide 1; C041086:gastric inhibitory polypeptide receptor; D005947:Glucose