title: Glucose sensing and signalling; regulation of intestinal glucose transport.
abstract: Epithelial cells lining the inner surface of the intestinal epithelium are in direct contact with a lumenal environment that varies dramatically with diet. It has long been suggested that the intestinal epithelium can sense the nutrient composition of lumenal contents. It is only recently that the nature of intestinal nutrient-sensing molecules and underlying mechanisms have been elucidated. There are a number of nutrient sensors expressed on the luminal membrane of endocrine cells that are activated by various dietary nutrients. We showed that the intestinal glucose sensor, T1R2+T1R3 and the G-protein, gustducin are expressed in endocrine cells. Eliminating sweet transduction in mice in vivo by deletion of either gustducin or T1R3 prevented dietary monosaccharide- and artificial sweetener-induced up-regulation of the Na+/glucose cotransporter, SGLT1 observed in wild-type mice. Transgenic mice, lacking gustducin or T1R3 had deficiencies in secretion of glucagon-like peptide 1 (GLP-1) and, glucose-dependent insulinotrophic peptide (GIP). Furthermore, they had an abnormal insulin profile and prolonged elevation of postprandial blood glucose in response to orally ingested carbohydrates. GIP and GLP-1 increase insulin secretion, while glucagon-like peptide 2 (GLP-2) modulates intestinal growth, blood flow and expression of SGLT1. The receptor for GLP-2 resides in enteric neurons and not in any surface epithelial cells, suggesting the involvement of the enteric nervous system in SGLT1 up-regulation. The accessibility of the glucose sensor and the important role that it plays in regulation of intestinal glucose absorption and glucose homeostasis makes it an attractive nutritional and therapeutic target for manipulation.
authors: Epithelial Function and Development Group, Department of Cellular and Molecular Physiology, Institute of Translational Medicine, Faculty of Health and Life Sciences, University of Liverpool, Liverpool L69 7ZJ, UK. spsb@liverpool.ac.uk
authors: S P
authors: SP
authors: Shirazi-Beechey
authors: A W
authors: AW
authors: Moran
authors: D J
authors: DJ
authors: Batchelor
authors: K
authors: K
authors: Daly
authors: M
authors: M
authors: Al-Rammahi
mesh_terms: D000818:Animals; D004040:Dietary Carbohydrates / Q000378:metabolism*; D017615:Enteric Nervous System / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D015398:Signal Transduction; D051269:Sodium-Glucose Transporter 1 / Q000378:metabolism; D015293:Transducin / Q000378:metabolism
chemical_list: D004040:Dietary Carbohydrates; D043562:Receptors, G-Protein-Coupled; D051269:Sodium-Glucose Transporter 1; C431926:taste receptors, type 1; C075192:gustducin; D015293:Transducin; D005947:Glucose