title: Cephalic phase insulin secretion is KATP channel independent.
abstract: Glucose-induced insulin secretion from pancreatic β-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 β-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.
authors.affiliation: Division of Cellular and Molecular Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Seino
authors.forename: Takashi
authors.initials: T
authors.lastname: Miki
authors.forename: Wakako
authors.initials: W
authors.lastname: Fujimoto
authors.forename: Eun
authors.initials: E
authors.lastname: Young Lee
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Kohtaro
authors.initials: K
authors.lastname: Minami
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Oiso
authors.forename: Susumu
authors.initials: S
authors.lastname: Seino
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D018679:Cholinergic Agonists / Q000494:pharmacology; D003912:Dextrins / Q000008:administration & dosage / Q000378:metabolism; D004040:Dietary Carbohydrates / Q000008:administration & dosage / Q000378:metabolism*; D004435:Eating; D005947:Glucose / Q000008:administration & dosage / Q000378:metabolism; D066298:In Vitro Techniques; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018727:Muscarinic Antagonists / Q000494:pharmacology; D010179:Pancreas / Q000187:drug effects / Q000294:innervation* / Q000378:metabolism; D010276:Parasympatholytics / Q000494:pharmacology; D010477:Perfusion; D019518:Postprandial Period; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics / Q000378:metabolism*; D013565:Sympatholytics / Q000494:pharmacology; D014630:Vagus Nerve / Q000187:drug effects / Q000378:metabolism*; D000099161:Kcnj11 Channel
chemical_list: D001786:Blood Glucose; D018679:Cholinergic Agonists; D003912:Dextrins; D004040:Dietary Carbohydrates; D005947:Glucose; D007328:Insulin; D018727:Muscarinic Antagonists; D010276:Parasympatholytics; D024661:Potassium Channels, Inwardly Rectifying; D013565:Sympatholytics; D000099161:Kcnj11 Channel
keywords: KATP channel; acetylcholine; cephalic phase insulin secretion