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Transformation of postingestive glucose responses after deletion of sweet taste receptor subunits or gastric bypass surgery.
- Source :
-
American journal of physiology. Endocrinology and metabolism [Am J Physiol Endocrinol Metab] 2012 Aug 15; Vol. 303 (4), pp. E464-74. Date of Electronic Publication: 2012 Jun 05. - Publication Year :
- 2012
-
Abstract
- The glucose-dependent secretion of the insulinotropic hormone glucagon-like peptide-1 (GLP-1) is a critical step in the regulation of glucose homeostasis. Two molecular mechanisms have separately been suggested as the primary mediator of intestinal glucose-stimulated GLP-1 secretion (GSGS): one is a metabotropic mechanism requiring the sweet taste receptor type 2 (T1R2) + type 3 (T1R3) while the second is a metabolic mechanism requiring ATP-sensitive K(+) (K(ATP)) channels. By quantifying sugar-stimulated hormone secretion in receptor knockout mice and in rats receiving Roux-en-Y gastric bypass (RYGB), we found that both of these mechanisms contribute to GSGS; however, the mechanisms exhibit different selectivity, regulation, and localization. T1R3(-/-) mice showed impaired glucose and insulin homeostasis during an oral glucose challenge as well as slowed insulin granule exocytosis from isolated pancreatic islets. Glucose, fructose, and sucralose evoked GLP-1 secretion from T1R3(+/+), but not T1R3(-/-), ileum explants; this secretion was not mimicked by the K(ATP) channel blocker glibenclamide. T1R2(-/-) mice showed normal glycemic control and partial small intestine GSGS, suggesting that T1R3 can mediate GSGS without T1R2. Robust GSGS that was K(ATP) channel-dependent and glucose-specific emerged in the large intestine of T1R3(-/-) mice and RYGB rats in association with elevated fecal carbohydrate throughout the distal gut. Our results demonstrate that the small and large intestines utilize distinct mechanisms for GSGS and suggest novel large intestine targets that could mimic the improved glycemic control seen after RYGB.
- Subjects :
- Animals
Cells, Cultured
Feces chemistry
Fructose pharmacology
Glucagon-Like Peptide 1 pharmacology
Glucose pharmacology
Glucose Tolerance Test
Glyburide pharmacology
Homeostasis drug effects
Homeostasis physiology
Hypoglycemic Agents pharmacology
Ileum drug effects
Ileum metabolism
Insulin metabolism
Insulin Secretion
Intestine, Large drug effects
Intestine, Large metabolism
Islets of Langerhans drug effects
Islets of Langerhans metabolism
KATP Channels metabolism
Mice
Rats
Sucrose analogs & derivatives
Sucrose pharmacology
Taste Buds drug effects
Gastric Bypass
Glucagon-Like Peptide 1 metabolism
Glucose metabolism
Receptors, G-Protein-Coupled metabolism
Taste Buds metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1522-1555
- Volume :
- 303
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- American journal of physiology. Endocrinology and metabolism
- Publication Type :
- Academic Journal
- Accession number :
- 22669246
- Full Text :
- https://doi.org/10.1152/ajpendo.00163.2012