title: Disordered control of intestinal sweet taste receptor expression and glucose absorption in type 2 diabetes.
abstract: We previously established that the intestinal sweet taste receptors (STRs), T1R2 and T1R3, were expressed in distinct epithelial cells in the human proximal intestine and that their transcript levels varied with glycemic status in patients with type 2 diabetes. Here we determined whether STR expression was 1) acutely regulated by changes in luminal and systemic glucose levels, 2) disordered in type 2 diabetes, and 3) linked to glucose absorption. Fourteen healthy subjects and 13 patients with type 2 diabetes were studied twice, at euglycemia (5.2 ± 0.2 mmol/L) or hyperglycemia (12.3 ± 0.2 mmol/L). Endoscopic biopsy specimens were collected from the duodenum at baseline and after a 30-min intraduodenal glucose infusion of 30 g/150 mL water plus 3 g 3-O-methylglucose (3-OMG). STR transcripts were quantified by RT-PCR, and plasma was assayed for 3-OMG concentration. Intestinal STR transcript levels at baseline were unaffected by acute variations in glycemia in healthy subjects and in type 2 diabetic patients. T1R2 transcript levels increased after luminal glucose infusion in both groups during euglycemia (+5.8 × 10(4) and +5.8 × 10(4) copies, respectively) but decreased in healthy subjects during hyperglycemia (-1.4 × 10(4) copies). T1R2 levels increased significantly in type 2 diabetic patients under the same conditions (+6.9 × 10(5) copies). Plasma 3-OMG concentrations were significantly higher in type 2 diabetic patients than in healthy control subjects during acute hyperglycemia. Intestinal T1R2 expression is reciprocally regulated by luminal glucose in health according to glycemic status but is disordered in type 2 diabetes during acute hyperglycemia. This defect may enhance glucose absorption in type 2 diabetic patients and exacerbate postprandial hyperglycemia.
authors.affiliation: Nerve-Gut Research Laboratory, University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Young
authors.forename: Bridgette
authors.initials: B
authors.lastname: Chia
authors.forename: Nicole J
authors.initials: NJ
authors.lastname: Isaacs
authors.forename: Jing
authors.initials: J
authors.lastname: Ma
authors.forename: Joan
authors.initials: J
authors.lastname: Khoo
authors.forename: Tongzhi
authors.initials: T
authors.lastname: Wu
authors.forename: Michael
authors.initials: M
authors.lastname: Horowitz
authors.forename: Christopher K
authors.initials: CK
authors.lastname: Rayner
mesh_terms: D019325:3-O-Methylglucose / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000378:metabolism*; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000503:physiopathology*; D004847:Epithelial Cells / Q000378:metabolism; D005215:Fasting; D005260:Female; D015309:Glucose Clamp Technique; D006442:Glycated Hemoglobin / Q000378:metabolism*; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism / Q000503:physiopathology*; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000473:pathology; D008297:Male; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*
chemical_list: D019325:3-O-Methylglucose; D001786:Blood Glucose; D002096:C-Peptide; D006442:Glycated Hemoglobin; D043562:Receptors, G-Protein-Coupled; C517652:hemoglobin A1c protein, human; C431926:taste receptors, type 1