title: Voltage-gated K+ channel KCNQ1 regulates insulin secretion in MIN6 β-cell line.
abstract: KCNQ1, located on 11p15.5, encodes a voltage-gated K(+) channel with six transmembrane regions, and loss-of-function mutations in the KCNQ1 gene cause hereditary long QT syndrome. Recent genetic studies have identified that single nucleotide polymorphisms located in intron 15 of the KCNQ1 gene are strongly associated with type 2 diabetes and impaired insulin secretion. In order to understand the role of KCNQ1 in insulin secretion, we introduced KCNQ1 into the MIN6 mouse β-cell line using a retrovirus-mediated gene transfer system. In KCNQ1 transferred MIN6 cells, both the density of the KCNQ1 current and the density of the total K(+) current were significantly increased. In addition, insulin secretion by glucose, pyruvate, or tolbutamide was significantly impaired by KCNQ1-overexpressing MIN6 cells. These results suggest that increased KCNQ1 protein expression limits insulin secretion from pancreatic β-cells by regulating the potassium channel current.
authors.affiliation: Department of Medical Biochemistry, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 860 8556, Japan. k-yamaga@kumamoto-u.ac.jp
authors.forename: Kazuya
authors.initials: K
authors.lastname: Yamagata
authors.forename: Takafumi
authors.initials: T
authors.lastname: Senokuchi
authors.forename: Meihong
authors.initials: M
authors.lastname: Lu
authors.forename: Makoto
authors.initials: M
authors.lastname: Takemoto
authors.forename: Md
authors.initials: M
authors.lastname: Fazlul Karim
authors.forename: Chisa
authors.initials: C
authors.lastname: Go
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Sato
authors.forename: Mitsutoki
authors.initials: M
authors.lastname: Hatta
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Yoshizawa
authors.forename: Eiichi
authors.initials: E
authors.lastname: Araki
authors.forename: Junichi
authors.initials: J
authors.lastname: Miyazaki
authors.forename: Wen-Jie
authors.initials: WJ
authors.lastname: Song
mesh_terms: D000818:Animals; D002460:Cell Line; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D051657:KCNQ1 Potassium Channel / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D012190:Retroviridae; D014162:Transfection
chemical_list: D007328:Insulin; D051657:KCNQ1 Potassium Channel; C496910:Kcnq1 protein, mouse; D052216:Glucagon-Like Peptide 1