Diabetes, Vol 42, Issue 12 1760-1772, Copyright © 1993 by American Diabetes Association

ARTICLES

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

P Ronner, FM Matschinsky, TL Hang, AJ Epstein and C Buettger
Department of Biochemistry and Biophysics, School of Medicine, University of Pennsylvania, Philadelphia 19104-6015.

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.
CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				J. Gromada, I. Franklin, and C. B. Wollheim {alpha}-Cells of the Endocrine Pancreas: 35 Years of Research but the Enigma Remains Endocr. Rev., February 1, 2007; 28(1): 84 - 116. [Abstract] [Full Text] [PDF]

				N. M. Doliba, W. Qin, M. Z. Vatamaniuk, C. W. Buettger, H. W. Collins, M. A Magnuson, K. H. Kaestner, D. F. Wilson, R. D. Carr, and F. M. Matschinsky Cholinergic regulation of fuel-induced hormone secretion and respiration of SUR1-/- mouse islets Am J Physiol Endocrinol Metab, September 1, 2006; 291(3): E525 - E535. [Abstract] [Full Text] [PDF]

				H. L. Olsen, S. Theander, K. Bokvist, K. Buschard, C. B. Wollheim, and J. Gromada Glucose Stimulates Glucagon Release in Single Rat {alpha}-Cells by Mechanisms that Mirror the Stimulus-Secretion Coupling in {beta}-Cells Endocrinology, November 1, 2005; 146(11): 4861 - 4870. [Abstract] [Full Text] [PDF]

				R. McGirr, C. E. Ejbick, D. E. Carter, J. D. Andrews, Y. Nie, T. C. Friedman, and S. Dhanvantari Glucose Dependence of the Regulated Secretory Pathway in {alpha}TC1-6 Cells Endocrinology, October 1, 2005; 146(10): 4514 - 4523. [Abstract] [Full Text] [PDF]

				C. Shiota, J. V. Rocheleau, M. Shiota, D. W. Piston, and M. A. Magnuson Impaired glucagon secretory responses in mice lacking the type 1 sulfonylurea receptor Am J Physiol Endocrinol Metab, October 1, 2005; 289(4): E570 - E577. [Abstract] [Full Text] [PDF]

				B. Raju and P. E. Cryer Loss of the Decrement in Intraislet Insulin Plausibly Explains Loss of the Glucagon Response to Hypoglycemia in Insulin-Deficient Diabetes: Documentation of the Intraislet Insulin Hypothesis in Humans Diabetes, March 1, 2005; 54(3): 757 - 764. [Abstract] [Full Text] [PDF]

				J. Gromada, X. Ma, M. Hoy, K. Bokvist, A. Salehi, P.-O. Berggren, and P. Rorsman ATP-Sensitive K+ Channel-Dependent Regulation of Glucagon Release and Electrical Activity by Glucose in Wild-Type and SUR1-/- Mouse {alpha}-Cells Diabetes, December 1, 2004; 53(suppl_3): S181 - S189. [Abstract] [Full Text] [PDF]

				R. A. Ritzel, J. B. Hansen, J. D. Veldhuis, and P. C. Butler Induction of {beta}-Cell Rest by a Kir6.2/SUR1-Selective KATP-Channel Opener Preserves {beta}-Cell Insulin Stores and Insulin Secretion in Human Islets Cultured at High (11 mM) Glucose J. Clin. Endocrinol. Metab., February 1, 2004; 89(2): 795 - 805. [Abstract] [Full Text] [PDF]

				O. Tschritter, M. Stumvoll, F. Machicao, M. Holzwarth, M. Weisser, E. Maerker, A. Teigeler, H. Haring, and A. Fritsche The Prevalent Glu23Lys Polymorphism in the Potassium Inward Rectifier 6.2 (KIR6.2) Gene Is Associated With Impaired Glucagon Suppression in Response to Hyperglycemia Diabetes, September 1, 2002; 51(9): 2854 - 2860. [Abstract] [Full Text] [PDF]

				P. Ronner, C. M. Naumann, and E. Friel Effects of Glucose and Amino Acids on Free ADP in {beta}HC9 Insulin-Secreting Cells Diabetes, February 1, 2001; 50(2): 291 - 300. [Abstract] [Full Text]

				C. Zhao, M. C. Wilson, F. Schuit, A. P. Halestrap, and G. A. Rutter Expression and Distribution of Lactate/Monocarboxylate Transporter Isoforms in Pancreatic Islets and the Exocrine Pancreas Diabetes, February 1, 2001; 50(2): 361 - 366. [Abstract] [Full Text]

				L. Aguilar-Bryan and J. Bryan Molecular Biology of Adenosine Triphosphate-Sensitive Potassium Channels Endocr. Rev., April 1, 1999; 20(2): 101 - 135. [Abstract] [Full Text]

				L Aguilar-Bryan, C. Nichols, S. Wechsler, J. Clement 4th, A. Boyd 3rd, G Gonzalez, H Herrera-Sosa, K Nguy, J Bryan, and D. Nelson Cloning of the beta cell high-affinity sulfonylurea receptor: a regulator of insulin secretion Science, April 21, 1995; 268(5209): 423 - 426. [Abstract] [PDF]