title: Mechanisms behind the immediate effects of Roux-en-Y gastric bypass surgery on type 2 diabetes.
abstract: BACKGROUND
  The most common bariatric surgery, Roux-en-Y gastric bypass, leads to glycemia normalization in most patients long before there is any appreciable weight loss. This effect is too large to be attributed purely to caloric restriction, so a number of other mechanisms have been proposed. The most popular hypothesis is enhanced production of an incretin, active glucagon-like peptide-1 (GLP-1), in the lower intestine. We therefore set out to test this hypothesis with a model which is simple enough to be robust and credible.
  
  
  METHODS
  Our method involves (1) setting up a set of time-dependent equations for the concentrations of the most relevant species, (2) considering an "adiabatic" (or quasi-equilibrium) state in which the concentrations are slowly varying compared to reaction rates (and which in the present case is a postprandial state), and (3) solving for the dependent concentrations (of e.g. insulin and glucose) as an independent concentration (of e.g. GLP-1) is varied.
  
  
  RESULTS
  Even in the most favorable scenario, with maximal values for (i) the increase in active GLP-1 concentration and (ii) the effect of GLP-1 on insulin production, enhancement of GLP-1 alone cannot account for the observations. I.e., the largest possible decrease in glucose predicted by the model is smaller than reported decreases, and the model predicts no decrease whatsoever in glucose ×insulin, in contrast to large observed decreases in homeostatic model assessment insulin resistance (HOMA-IR). On the other hand, both effects can be accounted for if the surgery leads to a substantial increase in some substance that opens an alternative insulin-independent pathway for glucose transport into muscle cells, which perhaps uses the same intracellular pool of GLUT-4 that is employed in an established insulin-independent pathway stimulated by muscle contraction during exercise.
  
  
  CONCLUSIONS
  Glycemia normalization following Roux-en-Y gastric bypass is undoubtedly caused by a variety of mechanisms, which may include caloric restriction, enhanced GLP-1, and perhaps others proposed in earlier papers on this subject. However, the present results suggest that another possible mechanism should be added to the list of candidates: enhanced production in the lower intestine of a substance which opens an alternative insulin-independent pathway for glucose transport.
authors.affiliation: Department of Physics and Astronomy, Texas A&M University, College Station, TX 77843, USA. allen@tamu.edu
authors.forename: Roland E
authors.initials: RE
authors.lastname: Allen
authors.forename: Tyler D
authors.initials: TD
authors.lastname: Hughes
authors.forename: Jia Lerd
authors.initials: JL
authors.lastname: Ng
authors.forename: Roberto D
authors.initials: RD
authors.lastname: Ortiz
authors.forename: Michel Abou
authors.initials: MA
authors.lastname: Ghantous
authors.forename: Othmane
authors.initials: O
authors.lastname: Bouhali
authors.forename: Philippe
authors.initials: P
authors.lastname: Froguel
authors.forename: Abdelilah
authors.initials: A
authors.lastname: Arredouani
mesh_terms: D001786:Blood Glucose / Q000032:analysis; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000503:physiopathology / Q000601:surgery*; D015390:Gastric Bypass; D006801:Humans; D007328:Insulin / Q000097:blood
chemical_list: D001786:Blood Glucose; D007328:Insulin