Journal
JOURNAL OF ENDOCRINOLOGY
Volume 218, Issue 1, Pages 25-33Publisher
BIOSCIENTIFICA LTD
DOI: 10.1530/JOE-12-0579
Keywords
K-ATP channel; cephalic phase insulin secretion; acetylcholine
Categories
Funding
- Ministry of Education, Culture, Sports, Science and Technology of Japan
Ask authors/readers for more resources
Glucose-induced insulin secretion from pancreatic beta-cells critically depends on the activity of ATP-sensitive K+ channels (K-ATP channel). We previously generated mice lacking Kir6.2, the pore subunit of the beta-cell K-ATP channel (Kir6.2(-/-)), that show almost no insulin secretion in response to glucose in vitro. In this study, we compared insulin secretion by voluntary feeding (self-motivated, oral nutrient ingestion) and by forced feeding (intra-gastric nutrient injection via gavage) in wild-type (Kir6.2(+/+)) and Kir6.2(-/-) mice. Under ad libitum feeding or during voluntary feeding of standard chow, blood glucose levels and plasma insulin levels were similar in Kir6.2(+/+) and Kir6.2(-/-) mice. By voluntary feeding of carbohydrate alone, insulin secretion was induced significantly in Kir6.2(-/-) mice but was markedly attenuated compared with that in Kir6.2(+/+) mice. On forced feeding of standard chow or carbohydrate alone, the insulin secretory response was markedly impaired or completely absent in Kir6.2(-/-) mice. Pretreatment with a muscarine receptor antagonist, atropine methyl nitrate, which does not cross the blood-brain barrier, almost completely blocked insulin secretion induced by voluntary feeding of standard chow or carbohydrate in Kir6.2(-/-) mice. Substantial glucose-induced insulin secretion was induced in the pancreas perfusion study of Kir6.2(-/-) mice only in the presence of carbamylcholine. These results suggest that a K-ATP channel-independent mechanism mediated by the vagal nerve plays a critical role in insulin secretion in response to nutrients in vivo.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available