| First Author | Seino Y | Year | 2013 |
| Journal | J Endocrinol | Volume | 218 |
| Issue | 1 | Pages | 25-33 |
| PubMed ID | 23608222 | Mgi Jnum | J:324416 |
| Mgi Id | MGI:6883994 | Doi | 10.1530/JOE-12-0579 |
| Citation | Seino Y, et al. (2013) Cephalic phase insulin secretion is KATP channel independent. J Endocrinol 218(1):25-33 |
| abstractText | Glucose-induced insulin secretion from pancreatic beta-cells critically depends on the activity of ATP-sensitive K(+) channels (KATP channel). We previously generated mice lacking Kir6.2, the pore subunit of the beta-cell KATP 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 KATP channel-independent mechanism mediated by the vagal nerve plays a critical role in insulin secretion in response to nutrients in vivo. |
