Small Intestinal Glucose Exposure Determines the Magnitude of the Incretin Effect in Health and Type 2 Diabetes

  1. Michael Horowitz, (MBBS, PhD, FRACP)
  1. Discipline of Medicine, University of Adelaide, Royal Adelaide Hospital, Adelaide, Australia, and Centre of Research Excellence (CRE) in Translating Nutritional Science to Good Health, University of Adelaide, Adelaide, Australia.
  1. Corresponding author: Michael Horowitz, Email: michael.horowitz{at}


The potential influence of gastric emptying on the ‘incretin effect’, mediated by glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), is unknown. The objectives of this study were to determine the effects of intraduodenal glucose infusions at 2 (ID2) and 4 (ID4) kcal/min (equating to two rates of gastric emptying within the physiological range) on the size of the incretin effect, gastrointestinal glucose disposal and plasma GIP, GLP-1 and glucagon, in health and type 2 diabetes. We studied 10 male BMI-matched controls and 11 male type 2 patients, managed by diet or metformin only. In both groups, GIP, GLP-1 and the magnitude of incretin effect were greater with ID4 than ID2, as was gastrointestinal glucose disposal; plasma glucagon was suppressed by ID2, but not ID4. There was no difference in the incretin effect between the two groups. Based on these data, we conclude that the rate of small intestinal glucose exposure (i.e. glucose load) is a major determinant of the comparative secretion of GIP and GLP-1, as well as the magnitude of the incretin effect and gastrointestinal glucose disposal in health and type 2 diabetes.

  • Received November 17, 2013.
  • Accepted March 27, 2014.

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