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Endocrinology, Vol 136, 464-467, Copyright © 1995 by Endocrine Society
ARTICLES |
P Krippeit-Drews, G Zempel, HP Ammon, F Lang and G Drews
Department of Physiology, University of Tubingen, Germany.
The membrane permeant thiol reagent diazene dicarboxylic acid bis-(N'- methylpiperazide) (DIP) has been shown to inhibit insulin secretion and Ca2+ uptake in pancreatic B cells in the presence of a stimulating glucose concentration (20 mM), whereas the nonpenetrating analog of DIP (bis-N'-methyliodide; DIP + 2) stimulates insulin release and Ca2+ uptake at a low glucose concentration (3 mM). The effects of DIP and DIP + 2 were tested on currents through ATP-sensitive K+ (K+ATP) channels and voltage-dependent Ca2+ channels (with Ba2+ as the charge carrier) in mouse pancreatic B cells in the whole-cell mode of the patch-clamp technique. DIP (0.1 mM) almost completely inhibited both the K+ATP and Ca2+ channel currents. In contrast, DIP + 2 (0.1 mM) did not affect the Ca2+ channel current but reduced the whole-cell K+ATP current by about 40%. The data strongly suggest that the suppression of insulin secretion previously observed with DIP is due to a reduction of the current through voltage-dependent Ca2+ channels, whereas the stimulation of hormone release induced by DIP + 2 is caused by the partial inhibition of K+ATP channel current.
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