title: Accelerated intestinal glucose absorption in morbidly obese humans: relationship to glucose transporters, incretin hormones, and glycemia.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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]).
  
  
  METHODS
  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.
authors.affiliation: Department of Gastroenterology and Hepatology (N.Q.N., T.L.D., J.E.B., C.K.R.), Royal Adelaide Hospital, Adelaide, South Australia 5000, Australia; Discipline of Medicine (N.Q.N., J.W., A.M.D., C.K.R., M.H., R.L.Y.), University of Adelaide, Royal Adelaide Hospital, Adelaide, South Australia 5000, Australia; Nerve-Gut Research Laboratory (B.C., R.L.Y.), Hanson Institute, Adelaide, South Australia, 5000, Australia; and Intensive Care Unit (A.M.D.), Royal Adelaide Hospital, Adelaide, South Australia 5000, Australia.
authors.forename: Nam Q
authors.initials: NQ
authors.lastname: Nguyen
authors.forename: Tamara L
authors.initials: TL
authors.lastname: Debreceni
authors.forename: Jenna E
authors.initials: JE
authors.lastname: Bambrick
authors.forename: Bridgette
authors.initials: B
authors.lastname: Chia
authors.forename: Judith
authors.initials: J
authors.lastname: Wishart
authors.forename: Adam M
authors.initials: AM
authors.lastname: Deane
authors.forename: Chris K
authors.initials: CK
authors.lastname: Rayner
authors.forename: Michael
authors.initials: M
authors.lastname: Horowitz
authors.forename: Richard L
authors.initials: RL
authors.lastname: Young
mesh_terms: D019325:3-O-Methylglucose / Q000493:pharmacokinetics; D000328:Adult; D001786:Blood Glucose / Q000378:metabolism*; D005260:Female; D005749:Gastric Inhibitory Polypeptide / Q000097:blood; D015870:Gene Expression; D005934:Glucagon / Q000097:blood; D052216:Glucagon-Like Peptide 1 / Q000097:blood; D005947:Glucose / Q000378:metabolism*; D051246:Glucose Transport Proteins, Facilitative / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D054795:Incretins / Q000097:blood*; D007328:Insulin / Q000097:blood; D007408:Intestinal Absorption; D008297:Male; D008875:Middle Aged; D009767:Obesity, Morbid / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors
chemical_list: D001786:Blood Glucose; D051246:Glucose Transport Proteins, Facilitative; D054795:Incretins; D007328:Insulin; D019325:3-O-Methylglucose; D005749:Gastric Inhibitory Polypeptide; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D005947:Glucose