Sulfonylurea-binding sites and ATP-sensitive K+ channels in α-TC glucagonoma and β-TC insulinoma cells

• Published in: Diabetes (New York, N.Y.) Vol. 42; no. 12; pp. 1760 - 1772
• Main Authors: RONNER, P, MATSCHINSKY, F. M, TU LE HANG, EPSTEIN, A. J, BUETTGER, C
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.12.1993
• Subjects: Adenosine Triphosphate - pharmacology; Animals; Binding Sites; Binding, Competitive; Biological and medical sciences; Diazoxide - pharmacology; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Glucagon; Glucagon - metabolism; Glucagonoma; Glyburide - metabolism; Hypoglycemic sulfonylureas; Insulinoma; Kinetics; Medical sciences; Membrane Potentials - drug effects; Mice; Pancreas; Pancreatic beta cells; Pancreatic Neoplasms; Pancreatic secretions; Physiological aspects; Potassium channels; Potassium Channels - drug effects; Potassium Channels - metabolism; Potassium Channels - physiology; Secretions; Sulfonylurea compounds; Sulfonylureas; Tolbutamide - pharmacology; Tritium; Tumor Cells, Cultured; Tumors. Hypoglycemia; Endocrinopathy; Human; Cell culture; Insulinoma; Ionic channel; Secretory tumor; B-Cell; Sulfonylureas; Glucagonoma; Digestive diseases; Tumor; Benign neoplasm; Endocrine pancreatic diseases; ATP; Potassium; Pancreatic disease
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/diab.42.12.1760

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.