Intestinal cholecystokinin controls glucose production through a neuronal network.
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.
Cheung
Grace W C
GW
Toronto General Research Institute, University Health Network, Toronto, Canada.
Kokorovic
Andrea
A
Lam
Carol K L
CK
Chari
Madhu
M
Lam
Tony K T
TK
D000818:Animals; D002766:Cholecystokinin / Q000378:metabolism*; D020109:Devazepide / Q000494:pharmacology; D004041:Dietary Fats / Q000494:pharmacology; D004386:Duodenum / Q000294:innervation / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D008297:Male; D009415:Nerve Net / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D043886:Receptor, Cholecystokinin A / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000378:metabolism*
D004041:Dietary Fats; D007328:Insulin; D043886:Receptor, Cholecystokinin A; D002766:Cholecystokinin; D005947:Glucose; D020109:Devazepide