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

TY - JOUR

T1 - GLUT2 and the incretin receptors are involved in glucose-induced incretin secretion

AU - Cani, Patrice D

AU - Holst, Jens Juul

AU - Drucker, Daniel J

AU - Delzenne, Nathalie M

AU - Thorens, Bernard

AU - Burcelin, Rémy

AU - Knauf, Claude

PY - 2007/9/30

Y1 - 2007/9/30

N2 - 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.

AB - 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.

KW - Animals

KW - Gastric Inhibitory Polypeptide

KW - Glucagon-Like Peptide 1

KW - Glucose

KW - Glucose Intolerance

KW - Glucose Tolerance Test

KW - Glucose Transporter Type 2

KW - Intestines

KW - Mice

KW - Mice, Knockout

KW - Models, Biological

KW - Portal System

KW - Receptors, Gastrointestinal Hormone

KW - Receptors, Glucagon

U2 - 10.1016/j.mce.2007.06.003

DO - 10.1016/j.mce.2007.06.003

M3 - Journal article

C2 - 17681422

SN - 0303-7207

VL - 276

SP - 18

EP - 23

JO - Molecular and Cellular Endocrinology

JF - Molecular and Cellular Endocrinology

IS - 1-2

ER -