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

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dc.contributor.authorYoung, R.
dc.contributor.authorChia, C.
dc.contributor.authorIsaacs, N.
dc.contributor.authorMa, J.
dc.contributor.authorKhoo, J.
dc.contributor.authorWu, T.
dc.contributor.authorHorowitz, M.
dc.contributor.authorRayner, C.
dc.date.issued2013
dc.description.abstractWe 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
dc.description.statementofresponsibilityRichard L. Young, Bridgette Chia, Nicole J. Isaacs, Jing Ma, Joan Khoo, Tongzhi Wu, Michael Horowitz, and Christopher K. Rayner
dc.identifier.citationDiabetes, 2013; 62(10):3532-3541
dc.identifier.doi10.2337/db13-0581
dc.identifier.issn0012-1797
dc.identifier.issn1939-327X
dc.identifier.orcidYoung, R. [0000-0001-5116-4951] [0009-0004-8274-9863]
dc.identifier.orcidWu, T. [0000-0003-1656-9210]
dc.identifier.orcidHorowitz, M. [0000-0002-0942-0306]
dc.identifier.orcidRayner, C. [0000-0002-5527-256X]
dc.identifier.urihttp://hdl.handle.net/2440/81219
dc.language.isoen
dc.publisherAmer Diabetes Assoc
dc.rights© 2013 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details
dc.source.urihttps://doi.org/10.2337/db13-0581
dc.subjectIntestines
dc.subjectIntestinal Mucosa
dc.subjectEpithelial Cells
dc.subjectHumans
dc.subjectDiabetes Mellitus, Type 2
dc.subjectHyperglycemia
dc.subjectC-Peptide
dc.subject3-O-Methylglucose
dc.subjectBlood Glucose
dc.subjectReceptors, G-Protein-Coupled
dc.subjectGlucose Clamp Technique
dc.subjectFasting
dc.subjectCross-Over Studies
dc.subjectIntestinal Absorption
dc.subjectFemale
dc.subjectMale
dc.subjectGlycated Hemoglobin
dc.titleDisordered control of intestinal sweet taste receptor expression and glucose absorption in type 2 diabetes
dc.typeJournal article
pubs.publication-statusPublished

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