Accelerated Intestinal Glucose Absorption in Morbidly Obese Humans: Relationship to Glucose Transporters, Incretin Hormones, and Glycemia

作者：Nguyen Nam Q^*; Debreceni Tamara L; Bambrick Jenna E; Chia Bridgette; Wishart Judith; Deane Adam M; Rayner Chris K; Horowitz Michael; Young Richard L

来源：Journal of Clinical Endocrinology & Metabolism, 2015, 100(3): 968-976.

DOI：10.1210/jc.2014-3144

Context: Intestinal glucose absorption is mediated by sodium-dependent glucose transporter 1 (SGLT-1) andglucose 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, glycemia, and incretin responses.
Design/Setting/Participants: Seventeen nondiabetic, morbidly obese subjects (body mass index [BMI], 48 +/- 4kg/m(2)) and 11 lean controls (BMI, 25 +/- 1 kg/m(2)) underwent endoscopic duodenal biopsies before and after a 30-minute intraduodenal glucose infusion (30 g glucose and 3 g 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 270 minutes. Expression of duodenal SGLT-1, GLUT2, and STR (T1R2) was quantified by PCR.
Results: The increase in plasma 3-OMG (P < .001) and blood glucose (P < .0001) were greater in obese than lean subjects. Plasma 3-OMG correlated directly with blood glucose (r = 0.78, P < .01). In response to intraduodenal glucose, plasma GIP (P < .001), glucagon (P < .001), and insulin (P < .001) were higher, but GLP-1 (P < .001) was less in the obese compared with lean. Expression of SGLT-1 (P = .035), but not GLUT2 or T1R2, was higher in the obese, and related to peak plasma 3-OMG (r = 0.60, P = .01), GIP (r = 0.67, P = .003), and insulin (r = 0.58, P = .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.

• 出版日期2015-3