Disordered Control of Intestinal Sweet Taste Receptor Expression and Glucose Absorption in Type 2 Diabetes
- Richard L. Young1,2,3,4⇑,
- Bridgette Chia1,4,
- Nicole J. Isaacs2,
- Jing Ma2,5,
- Joan Khoo2,6,
- Tongzhi Wu2,3,
- Michael Horowitz2,3 and
- Christopher K. Rayner2,3,4
- 1Nerve-Gut Research Laboratory, University of Adelaide, Adelaide, South Australia, Australia
- 2Discipline of Medicine, University of Adelaide, Adelaide, South Australia, Australia
- 3Centre of Research Excellence in Translating Nutritional Science to Good Health, University of Adelaide, Adelaide, South Australia, Australia
- 4Department of Gastroenterology and Hepatology, Royal Adelaide Hospital, Adelaide, South Australia, Australia
- 5Department of Endocrinology and Metabolism, Shanghai Renji Hospital, Shanghai Jiaotong University, Shanghai, China
- 6Department of Endocrinology, Changi General Hospital, Singapore.
- Corresponding author: Richard L. Young, .
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 × 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 diabetic patients under the same conditions (+6.9 × 105 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.
- Received April 11, 2013.
- Accepted June 5, 2013.
- © 2013 by the American Diabetes Association.
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