Cholecystokinin (CCK) is a gut peptide involved in the regulation of energy homeostasis by duodenal lipids via a neuronal network. However, it is unknown whether CCK also regulates glucose homeostasis through a neuronal network. Using an in vivo rat model, we demonstrated that duodenal CCK-8 (biologically active form of CCK) can lower glucose production through the activation of a gut-brain-liver axis via CCK-A receptors, and this glucose-regulatory effect is physiologically relevant. Since duodenal lipids can also lower glucose production through a gut-brain-liver axis, we verified that this duodenal-lipid effect is mediated by CCK-A receptor activation. Lastly, in rats fed on a high-fat diet for three days, duodenal CCK failed to suppress glucose production, suggesting a state of CCK-resistance. In summary, these findings revealed that intestinal CCK can regulate glucose homeostasis through a neuronal network and suggest that intestinal CCK resistance may contribute to hyperglycemia in response to high-fat feeding.
| Identifer | oai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/33714 |
| Date | 03 December 2012 |
| Creators | Cheung, Wing Chee |
| Contributors | Lam, Tony K. T. |
| Source Sets | University of Toronto |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis |
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