Accelerated intestinal glucose absorption in morbidly obese humans: relationship to glucose transporters, incretin hormones, and glycemia

J Clin Endocrinol Metab. 2015 Mar;100(3):968-76. doi: 10.1210/jc.2014-3144. Epub 2014 Nov 25.

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, glycemia, and incretin responses.

Design/setting/participants: Seventeen nondiabetic, morbidly obese subjects (body mass index [BMI], 48 ± 4 kg/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.

Publication types

  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3-O-Methylglucose / pharmacokinetics
  • Adult
  • Blood Glucose / metabolism*
  • Female
  • Gastric Inhibitory Polypeptide / blood
  • Gene Expression
  • Glucagon / blood
  • Glucagon-Like Peptide 1 / blood
  • Glucose / metabolism*
  • Glucose Transport Proteins, Facilitative / genetics*
  • Glucose Transport Proteins, Facilitative / metabolism
  • Humans
  • Incretins / blood*
  • Insulin / blood
  • Intestinal Absorption*
  • Male
  • Middle Aged
  • Obesity, Morbid / genetics
  • Obesity, Morbid / metabolism*
  • Time Factors

Substances

  • Blood Glucose
  • Glucose Transport Proteins, Facilitative
  • Incretins
  • Insulin
  • 3-O-Methylglucose
  • Gastric Inhibitory Polypeptide
  • Glucagon-Like Peptide 1
  • Glucagon
  • Glucose