Intestinal Cholecystokinin Controls Glucose Production Through a Neuronal Network

Cell Metab. 2009 Aug;10(2):99-109. doi: 10.1016/j.cmet.2009.07.005.


Cholecystokinin (CCK) is a peptide hormone that is released from the gut in response to nutrients such as lipids to lower food intake. Here we report that a primary increase of CCK-8, the biologically active form of CCK, in the duodenum lowers glucose production independent of changes in circulating insulin levels. Furthermore, we show that duodenal CCK-8 requires the activation of the gut CCK-A receptor and a gut-brain-liver neuronal axis to lower glucose production. Finally, duodenal CCK-8 fails to lower glucose production in the early onset of high-fat diet-induced insulin resistance. These findings reveal a role for gut CCK that lowers glucose production through a neuronal network and suggest that intestinal CCK resistance may contribute to hyperglycemia in response to high-fat feeding.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cholecystokinin / metabolism*
  • Devazepide / pharmacology
  • Dietary Fats / pharmacology
  • Duodenum / innervation
  • Duodenum / metabolism*
  • Glucose / metabolism*
  • Insulin / metabolism
  • Insulin Resistance
  • Male
  • Nerve Net / physiology*
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Cholecystokinin A / antagonists & inhibitors
  • Receptor, Cholecystokinin A / deficiency
  • Receptor, Cholecystokinin A / metabolism*


  • Dietary Fats
  • Insulin
  • Receptor, Cholecystokinin A
  • Cholecystokinin
  • Glucose
  • Devazepide