P. Krippeitdrews et al., EFFECTS OF MEMBRANE PERMEANT AND IMPERMEANT THIOL REAGENTS ON CA2-CELLS( AND K+ CHANNEL CURRENTS OF MOUSE PANCREATIC B), Endocrinology, 136(2), 1995, pp. 464-467
The membrane permeant thiol reagent diazene dicarboxylic acid bis-(N'-
methylpiperazide) (DIP) has been shown to inhibit insulin secretion an
d Ca2+ uptake in pancreatic B cells in the presence of a stimulating g
lucose concentration (20 mM), whereas the nonpenetrating analog of DIP
(bis-N'-methyliodide; DIP+2) stimulates insulin release and Ca2+ upta
ke 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 a
nd voltage-dependent Ca2+ channels (with Ba2+ as the charge carrier) i
n mouse pancreatic B cells in the whole-cell mode of the patch-clamp t
echnique. DIP (0.1 mM) almost completely inhibited both the K-ATP(+) a
nd 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 b
y about 40%. The data strongly suggest that the suppression of insulin
secretion previously observed with DIP is due to a reduction of the c
urrent through voltage-dependent Ca2+ channels, whereas the stimulatio
n of hormone release induced by DIP+2 is caused by the partial inhibit
ion of K-ATP(+) channel current.