Sulfonylurea-binding sites and ATP-sensitive K+ channels in alpha-TC glucagonoma and beta-TC insulinoma cells

• Published in: Diabetes (New York, N.Y.) Vol. 42; no. 12; pp. 1760 - 1772
• Main Authors: Ronner, P., Matschinsky, F. M., Hang, T. L., Epstein, A. J., Buettger, C.
• Format: Journal Article
• Language: English
• Published: American Diabetes Association 01-12-1993
• ISSN: 0012-1797; 1939-327X; 0012-1797
• DOI: 10.2337/diabetes.42.12.1760

Sulfonylurea-binding sites and ATP-sensitive K+ channels in alpha-TC glucagonoma and beta-TC insulinoma cells.
P Ronner ,
F M Matschinsky ,
T L Hang ,
A J Epstein and
C Buettger
Department of Biochemistry and Biophysics, School of Medicine, University of Pennsylvania, Philadelphia 19104-6015.
Abstract
alpha-Cells secrete glucagon in a fuel-dependent fashion. We tested the hypothesis that alpha-cells contain sulfonylurea-
and ATP-sensitive K+ channels. We studied two clonal lines of alpha-TC cells (simian virus 40 T-antigen induced glucagonoma
cells) and for reference purposes, similarly transformed beta-TC insulinoma cells. alpha-TC cells each contained approximately
3000 high-affinity binding sites for the sulfonylurea [3H]glyburide. Whole-cell ATP- and tolbutamide-sensitive K+ currents
of alpha-TC and beta-TC cells, relative to cell surface area, were comparable. In cell-attached membrane patches of alpha-TC
cells, two types of K+ channels were observed. They had slope conductances of approximately 63 and 33 pS when the electrode
contained 151 mM K+. Tolbutamide and diazoxide decreased and enhanced, respectively, the open probability of these channels.
The membrane of alpha-TC cells depolarized periodically. This electrical activity was inhibited by diazoxide. A physiological
mixture of amino acids enhanced glucagon release, and high glucose partially inhibited this release. Tolbutamide also enhanced
glucagon release, whereas diazoxide inhibited it. Thus, alpha-TC glucagonoma cells contain ATP-sensitive K+ channels that
regulate glucagon release, yet allow inhibition of hormone release by glucose.