Role of aryl hydrocarbon receptor nuclear translocator in KATP channel-mediated insulin secretion in INS-1 insulinoma cells

Biochemical and Biophysical Research Communications
Ji-Seon KimYang-Sook Chun

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.

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Citations

Jun 12, 2014·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Andrew J Murray, Hugh E Montgomery
Dec 17, 2014·Trends in Endocrinology and Metabolism : TEM·Paul V Sabatini, Francis C Lynn
Jan 14, 2020·Biochimica Et Biophysica Acta. Molecular Cell Research·Alban GiraultHalima Ouadid-Ahidouch
Jun 19, 2021·Pflügers Archiv : European journal of physiology·Hae Young Yoo, Sung Joon Kim

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