ATP-sensitive potassium channels and efaroxan-induced insulin release in the electrofusion-derived BRIN-BD11 beta-cell line

JC Chapman, Neville McClenaghan, KE Cosgrove, MN Hashmi, RM Shepherd, AN Giesberts, SJ White, C Ammala, Peter Flatt, MJ Dunne

Research output: Contribution to journalArticlepeer-review


The properties of ATP-sensitive K+ (K-ATP) channels were explored in the electrofusion-derived, glucose-responsive, insulin-secreting cell line BRIN-BD11 using patch-clamp techniques. In intact cells, K-ATP channels were inhibited by glucose, the sulfonylurea tolbutamide, and the imidazoline compounds efaroxan and phentolamine, Each of these agents initiated insulin secretion and potentiated the actions of glucose. K-ATP channels were blocked by ATP in a concentration-dependent manner and activated by ADP in the presence of ATP. In both intact cells and excised inside-out patches, the K-ATP channel agonists diazoxide and pinacidil activated channels, and both compounds inhibited insulin secretion evoked by glucose, tolbutamide, and imidazolines. The mechanisms of action of imidazolines were examined in more detail. Pre-exposure of BRIN-BD11 cells to either efaroxan or phentolamine selectively inhibited imidazoline-induced insulin secretion but not the secretory responses of cells to glucose, tolbutamide, or a depolarizing concentration of KCI. These conditions did not result in the loss of depolarization-dependent rises in intracellular Ca2+ ([Ca2+](i)), K-ATP channel operation, or the actions of either ATP or efaroxan on K-ATP channels. Desensitization of the imidazoline receptor following exposure to high concentrations of efaroxan, however, was found to result in an increase in SUR1 protein expression and, as a consequence, an upregulation of K-ATP channel density. Our data protide 1) the first characterization of K-ATP channels in BRIN-BD11 cells, a novel insulin-secreting cell Line produced by electrofusion techniques, and 2) a further analysis of the role of imidazolines in the control of insulin release.
Original languageEnglish
Pages (from-to)2349-2357
Issue number12
Publication statusPublished (in print/issue) - Dec 1999


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