Role of aryl hydrocarbon receptor nuclear translocator in KATP channel-mediated insulin secretion in INS-1 insulinoma cells.
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.
Kim
Ji-Seon
JS
Department of Physiology, Seoul National University College of Medicine, 28 Yongon-dong, Chongno-gu, Seoul 110-799, Republic of Korea.
Zheng
Haifeng
H
Kim
Sung Joon
SJ
Park
Jong-Wan
JW
Park
Kyong Soo
KS
Ho
Won-Kyung
WK
Chun
Yang-Sook
YS
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
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