S-Space College of Medicine/School of Medicine (의과대학/대학원) Pharmacology (약리학전공) Journal Papers (저널논문_약리학전공)
Role of aryl hydrocarbon receptor nuclear translocator in KATP channel-mediated insulin secretion in INS-1 insulinoma cells
- Kim, Ji-Seon; Zheng, Haifeng; Kim, Sung Joon; Park, Jong-Wan; Park, Kyong Soo; Ho, Won-Kyung; Chun, Yang-Sook
- Issue Date
- Biochem Biophys Res Commun. 379 (2009) 1048-1053
- Animals; Aryl Hydrocarbon Receptor Nuclear Translocator/genetics/*metabolism; Basic Helix-Loop-Helix Transcription Factors/metabolism; Cell Line, Tumor; Gene Knockdown Techniques; Glucose/pharmacology; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism; Insulin/*secretion; Insulin-Secreting Cells/drug effects/*secretion; Insulinoma; Potassium Channels/*biosynthesis/genetics; Potassium Channels, Inwardly Rectifying/*biosynthesis/genetics; Rats
- 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.
- 1090-2104 (Electronic)
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