The role of the gut hormone GLP-1 in the metabolic improvements caused by ileal transposition

Background: Bariatric surgery alters the gastrointestinal hormonal milieu leading to improved glucose homeostasis, though the mechanism leading to these changes is poorly understood. Ileal transposition ( IT) is a procedure that is neither restrictive nor mal-absorptive but nevertheless produces profound improvements in glucose regulation. Ileal transposition involves a short segment of distal ileum being transposed to the proximal jejunum in an isoperistaltic direction, thereby avoiding any gastric resection or intestinal bypass. Methods: Diet-induced obese rats underwent either ileal transposition ( IT) or Sham procedures. The Sham operated rats were pair-fed to the IT surgical group to control for the effects of reduced food intake. Body composition data were recorded at specific time points, and glucose tolerance tests were performed at 5 and 6 wk, both in the presence and absence of Exendin 9-39, a known glucose-like peptide 1 (GLP-1) receptor antagonist. A subset of naive rats were also maintained for comparison. Results: IT and Sham operated rats had no differences in food intake and body weight, however, IT rats had a significant decrease in their body fat composition ( P < 0.05). No difference existed in glucose tolerance when exposed to an intraperitoneal glucose load, however, IT rats showed markedly improved glucose tolerance when submitted to an oral glucose tolerance test ( P < 0.001). Blocking GLP-1 receptors reversed these important improvements in rats with IT surgery. Conclusions: The present work recapitulates what is seen in rodents and humans that IT improves glucose tolerance and body composition. The present data provide compelling evidence that these improvements are a product of increased GLP-1 secretion that results from placing the key GLP-1 secreting cells closer to chyme coming from the stomach. Such data support the notion that rather than restriction or malabsorption, the underling molecular mechanisms that mediate the potent improvements produced by bariatric procedures involve increased activation of GLP-1 signaling. (C) 2012 Elsevier Inc. All rights reserved.