Nutrient-Sensing Mechanisms in the Gut as Therapeutic Targets for Diabetes

  1. Tony K.T. Lam1,2,3,5
  1. 1Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada
  2. 2Department of Medicine, University of Toronto, Toronto, Ontario, Canada
  3. 3Department of Physiology, University of Toronto, Toronto, Ontario, Canada
  4. 4Department of Cardiovascular, Metabolic and Endocrine Diseases, Pfizer Global Research and Development, Cambridge, Massachusetts
  5. 5Banting and Best Diabetes Centre, University of Toronto, Toronto, Ontario, Canada
  1. Corresponding author: Tony K.T. Lam, tony.lam{at}uhnres.utoronto.ca.
  1. D.M.B. and B.A.R. contributed equally to the study.

Abstract

The small intestine is traditionally viewed as an organ that mediates nutrient digestion and absorption. This view has recently been revised owing to the ability of the duodenum to sense nutrient influx and trigger negative feedback loops to inhibit glucose production and food intake to maintain metabolic homeostasis. Further, duodenal nutrient-sensing defects are acquired in diabetes and obesity, leading to increased glucose production. In contrast, jejunal nutrient sensing inhibits glucose production and mediates the early antidiabetic effect of bariatric surgery, and gut microbiota composition may alter intestinal nutrient-sensing mechanisms to regain better control of glucose homeostasis in diabetes and obesity in the long term. This perspective highlights nutrient-sensing mechanisms in the gut that regulate glucose homeostasis and the potential of targeting gut nutrient-sensing mechanisms as a therapeutic strategy to lower blood glucose concentrations in diabetes.

  • Received April 2, 2013.
  • Accepted May 20, 2013.

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