Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/92563
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Type: Journal article
Title: Accelerated intestinal glucose absorption in morbidly obese humans: relationship to glucose transporters, incretin hormones, and glycaemia
Author: Nguyen, N.
Debreceni, T.
Bambrick, J.
Chia, B.
Wishart, J.
Deane, A.
Rayner, C.
Horowitz, M.
Young, R.
Citation: Journal of Clinical Endocrinology and Metabolism, 2014; 100(3):968-976
Publisher: Endocrine Society
Issue Date: 2014
ISSN: 0021-972X
1945-7197
Statement of
Responsibility: 
Nam Q. Nguyen, Tamara L. Debreceni, Jenna E. Bambrick, Bridgette Chia, Judith Wishart, Adam M. Deane, Chris K. Rayner, Michael Horowitz, and Richard L. Young
Abstract: Context: Intestinal glucose absorption is mediated by sodium dependent glucose transporter-1 (SGLT-1) and glucose transporter-2 (GLUT2), which are linked to sweet taste receptor (STR) signaling and incretin responses. Objective: This study aimed to examine intestinal glucose absorption in morbidly obese humans, and its relationship to the expression of STR and glucose transporters, glycaemia, and incretin responses. Design/Setting/Participants: 17 non-diabetic, morbidly obese subjects (BMI:48±4kg/m(2)) and 11 lean controls (BMI:25±1kg/m(2)) underwent endoscopic duodenal biopsies before and after a 30-min intraduodenal glucose infusion (30g glucose & 3g 3-O-methylglucose (3-OMG)). Main Outcome Measures: Blood glucose and plasma concentrations of 3-OMG, glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), insulin, and glucagon were measured over 270min. Expression of duodenal SGLT-1, GLUT2 and STR was quantified by PCR. Results: The rise in plasma 3-OMG (P<0.001) and blood glucose (P<0.0001) were greater in obese than lean subjects. Plasma 3-OMG correlated directly with blood glucose (r=0.78, P<0.01). In response to intraduodenal glucose, plasma GIP (P<0.001), glucagon (P<0.001), and insulin (P<0.001) were higher, but GLP-1 (P<0.001) was less, in the obese compared to lean. Expression of SGLT-1 (P=0.035), but not GLUT2 or T1R2, was higher in the obese, and related to peak plasma 3-OMG (r=0.60, P=0.01), GIP (r=0.67, P=0.003) and insulin (r=0.58, P=0.02). Conclusions: In morbid obesity, proximal intestine glucose absorption is accelerated and related to increased SGLT-1 expression, leading to an incretin-glucagon profile promoting hyperinsulinemia and hyperglycemia. These findings are consistent with the concept that accelerated glucose absorption in the proximal gut underlies the foregut theory of obesity and type 2 diabetes.
Keywords: Humans
Description: Published Online: November 25, 2014
Rights: Copyright © 2015 by the Endocrine Society
RMID: 0030016480
DOI: 10.1210/jc.2014-3144
Appears in Collections:Medicine publications

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