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Diabetes, Vol 40, Issue 7 885-892, Copyright © 1991 by American Diabetes Association

ARTICLES

Inhibition of ATP-sensitive K+ channels in pancreatic beta-cells by nonsulfonylurea drug linogliride

P Ronner, TJ Higgins and GA Kimmich
Department of Biochemistry and Biophysics, School of Medicine, University of Pennsylvania, Philadelphia 19104.

Linogliride is a nonsulfonylurea drug that lowers blood glucose levels in nondiabetic and diabetic humans and animals. Linogliride also stimulates insulin release in vitro. In the perfused pancreas, pretreatment with tolbutamide desensitizes beta-cells to the action of linogliride. We tested the hypothesis that linogliride, like tolbutamide, affects the activity of ATP-sensitive K+ channels, which are thought to control insulin release. We used the whole-cell voltage-clamping technique to measure the K+ current through ATP-sensitive K+ channels in the plasma membrane of single rat beta-cells, which were dialyzed with 30 microM ATP. Linogliride (10-300 microM) inhibited the K+ current; half-maximal inhibition was observed at 6-25 microM, depending on how much time was allowed for equilibration of the drug. Reversal of the inhibition was slow (t1/2 approximately 4 min). In summary, linogliride leads to a decrease in the activity of ATP-sensitive K+ channels.
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Diabetes Diabetes Care Clinical Diabetes Diabetes Spectrum
Copyright © 1991 by the American Diabetes Association.