title: Role of aryl hydrocarbon receptor nuclear translocator in KATP channel-mediated insulin secretion in INS-1 insulinoma cells.
abstract: Aryl hydrocarbon receptor nuclear translocator (ARNT) has been known to participate in cellular responses to xenobiotic and hypoxic stresses, as a common partner of aryl hydrocarbon receptor and hypoxia inducible factor-1/2alpha. Recently, it was reported that ARNT is essential for adequate insulin secretion in response to glucose input and that its expression is downregulated in the pancreatic islets of diabetic patients. In the present study, the authors addressed the mechanism by which ARNT regulates insulin secretion in the INS-1 insulinoma cell line. In ARNT knock-down cells, basal insulin release was elevated, but insulin secretion was not further stimulated by a high-glucose challenge. Electrophysiological analyses revealed that glucose-dependent membrane depolarization was impaired in these cells. Furthermore, K(ATP) channel activity and expression were reduced. Of two K(ATP) channel subunits, Kir6.2 was found to be positively regulated by ARNT at the mRNA and protein levels. Based on these results, the authors suggest that ARNT expresses K(ATP) channel and by so doing regulates glucose-dependent insulin secretion.
authors.affiliation: Department of Physiology, Seoul National University College of Medicine, 28 Yongon-dong, Chongno-gu, Seoul 110-799, Republic of Korea.
authors.forename: Ji-Seon
authors.initials: JS
authors.lastname: Kim
authors.forename: Haifeng
authors.initials: H
authors.lastname: Zheng
authors.forename: Sung Joon
authors.initials: SJ
authors.lastname: Kim
authors.forename: Jong-Wan
authors.initials: JW
authors.lastname: Park
authors.forename: Kyong Soo
authors.initials: KS
authors.lastname: Park
authors.forename: Won-Kyung
authors.initials: WK
authors.lastname: Ho
authors.forename: Yang-Sook
authors.initials: YS
authors.lastname: Chun
mesh_terms: D000818:Animals; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator / Q000235:genetics / Q000378:metabolism*; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D055785:Gene Knockdown Techniques; D005947:Glucose / Q000494:pharmacology; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism*; D007340:Insulinoma; D015221:Potassium Channels / Q000096:biosynthesis* / Q000235:genetics; D024661:Potassium Channels, Inwardly Rectifying / Q000096:biosynthesis* / Q000235:genetics; D051381:Rats; D000099162:Endothelial PAS Domain-Containing Protein 1; D000099161:Kcnj11 Channel
chemical_list: D051784:Aryl Hydrocarbon Receptor Nuclear Translocator; D051792:Basic Helix-Loop-Helix Proteins; D005947:Glucose; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007328:Insulin; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D000099162:Endothelial PAS Domain-Containing Protein 1; D000099161:Kcnj11 Channel; C497444:Hif1a protein, rat; C117780:mitochondrial K(ATP) channel