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

Intestinal cholecystokinin controls glucose production through a neuronal network.

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  • 1Toronto General Research Institute, University Health Network, Toronto, Canada.


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.

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