Disordered control of intestinal sweet taste receptor expression and glucose absorption in type 2 diabetes

  1. Christopher K Rayner2,3,4
  1. 1Nerve-Gut Research Laboratory and
  2. 2Discipline of Medicine, University of Adelaide, Adelaide, South Australia, 5000;
  3. 3Centre of Research Excellence in Translating Nutritional Science to Good Health, University of Adelaide;
  4. 4Department of Gastroenterology & Hepatology, Royal Adelaide Hospital, Adelaide, South Australia 5000, Australia;
  5. 5Department of Endocrinology & Metabolism, Shanghai Renji Hospital, Shanghai Jiaotong University 200127, China;
  6. 6Department of Endocrinology, Changi General Hospital 529889, Singapore.
  1. Corresponding author: Dr Richard L Young richard.young{at}adelaide.edu.au

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 (i) acutely regulated by changes in luminal and systemic glucose levels, (ii) disordered in type 2 diabetes, and (iii) 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 biopsies were collected from the duodenum at baseline and after a 30 min intraduodenal glucose infusion (30 g/150 ml water plus 3 g 3-O-methylglucose, 3-OMG). STR transcripts were quantified by RT-PCR and plasma assayed for 3-OMG concentration. Intestinal STR transcript levels at baseline were unaffected by acute variations in glycemia in healthy subjects and type 2 patients. T1R2 transcript levels increased after luminal glucose infusion in both groups during euglycemia (+5.8 × 104 and +5.8 × 104 copies, respectively), but decreased in healthy subjects during hyperglycemia (-1.4 × 104 copies). T1R2 levels increased significantly in type 2 patients under the same conditions (+6.9 × 105 copies). Plasma 3-OMG concentrations were significantly higher in type 2 patients than healthy controls 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 patients and exacerbate postprandial hyperglycemia.

  • Received April 11, 2013.
  • Accepted June 5, 2013.

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This Article

  1. Diabetes
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