Role of the foregut in the early improvement in glucose tolerance and insulin sensitivity following Roux-en-Y gastric bypass surgery

Erik N. Hansen, Robyn A. Tamboli, James M. Isbell, Jabbar Saliba, Julia P. Dunn, Pamela A. Marks-Shulman, Naji N. Abumrad

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70 Scopus citations


Bypass of the foregut following Roux-en-Y gastric bypass (RYGB) surgery results in altered nutrient absorption, which is proposed to underlie the improvement in glucose tolerance and insulin sensitivity. We conducted a prospective crossover study in which a mixed meal was delivered orally before RYGB (gastric) and both orally (jejunal) and by gastrostomy tube (gastric) postoperatively (1 and 6 wk) in nine subjects. Glucose, insulin, and incretin responses were measured, and whole-body insulin sensitivity was estimated with the insulin sensitivity index composite. RYGB resulted in an improved glucose, insulin, and glucagon-like peptide-1 (GLP-1) area under the curve (AUC) in the first 6 wk postoperatively (all P ≤ 0.018); there was no effect of delivery route (all P ≥ 0.632) or route × time interaction (all P ≥ 0.084). The glucose-dependent insulinotropic polypeptide (GIP) AUC was unchanged after RYGB (P = 0.819); however, GIP levels peaked earlier after RYGB with jejunal delivery. The ratio of insulin AUC to GLP-1 and GIP AUC decreased after surgery (P =.001 and 0.061, respectively) without an effect of delivery route over time (both P ≥ 0.646). Insulin sensitivity improved post-RYGB (P = 0.001) with no difference between the gastric and jejunal delivery of the mixed meal over time (P = 0.819). These data suggest that exclusion of nutrients from the foregut with RYGB does not improve glucose tolerance or insulin sensitivity. However, changes in the foregut response post-RYGB due to lack of nutrient exposure cannot be excluded. Our findings suggest that foregut bypass may alter the incretin response by enhanced nutrient delivery to the hindgut.

Original languageEnglish (US)
Pages (from-to)G795-G802
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Issue number5
StatePublished - May 2011
Externally publishedYes


  • Gastrostomy tube
  • Incretin
  • Mixed meal

ASJC Scopus subject areas

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)


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