HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ravier, M. A. Articles by Henquin, J.-C. Search for Related Content PubMed PubMed Citation Articles by Ravier, M. A. Articles by Henquin, J.-C. Social Bookmarking                      What's this?

J Biol Chem, Vol. 275, Issue 3, 1587-1593, January 21, 2000

The Oscillatory Behavior of Pancreatic Islets from Mice with Mitochondrial Glycerol-3-phosphate Dehydrogenase Knockout^*

Magalie A. Ravier, Kazuhiro Eto^§, Françoise C. Jonkers, Myriam Nenquin, Takashi Kadowaki^§, and Jean-Claude Henquin^¶

From the  Unité d'Endocrinologie et Métabolisme, University of Louvain Faculty of Medicine, B-1200 Brussels, Belgium and the ^§ Department of Metabolic Diseases, Graduate School of Medicine, University of Tokyo, Bunkyo-ku, Tokyo 113-8655, Japan

Glucose stimulation of pancreatic  cells induces oscillations of the membrane potential, cytosolic Ca²⁺ ([Ca²⁺]_i), and insulin secretion. Each of these events depends on glucose metabolism. Both intrinsic oscillations of metabolism and repetitive activation of mitochondrial dehydrogenases by Ca²⁺ have been suggested to be decisive for this oscillatory behavior. Among these dehydrogenases, mitochondrial glycerol-3-phosphate dehydrogenase (mGPDH), the key enzyme of the glycerol phosphate NADH shuttle, is activated by cytosolic [Ca²⁺]_i. In the present study, we compared different types of oscillations in  cells from wild-type and mGPDH^/ mice. In clusters of 5-30 islet cells and in intact islets, 15 mM glucose induced an initial drop of [Ca²⁺]_i, followed by an increase in three phases: a marked initial rise, a partial decrease with rapid oscillations and eventually large and slow oscillations. These changes, in particular the frequency of the oscillations and the magnitude of the [Ca²⁺] rise, were similar in wild-type and mGPDH^/ mice. Glucose-induced electrical activity (oscillations of the membrane potential with bursts of action potentials) was not altered in mGPDH^/  cells. In single islets from either type of mouse, insulin secretion strictly followed the changes in [Ca²⁺]_i during imposed oscillations induced by pulses of high K⁺ or glucose and during the biphasic elevation induced by sustained stimulation with glucose. An imposed and controlled rise of [Ca²⁺]_i in  cells similarly increased NAD(P)H fluorescence in control and mGDPH^/ islets. Inhibition of the malate-aspartate NADH shuttle with aminooxyacetate only had minor effects in control islets but abolished the electrical, [Ca²⁺]_i and secretory responses in mGPDH^/ islets. The results show that the two distinct NADH shuttles play an important but at least partially redundant role in glucose-induced insulin secretion. The oscillatory behavior of  cells does not depend on the functioning of mGPDH and on metabolic oscillations that would be generated by cyclic activation of this enzyme by Ca²⁺.

---

^* This work was supported by Grant 3.4552.98 from the Fonds de la Recherche Scientifique Médicale (Brussels), Grant 95/00-188 from the General Direction of Scientific Research of the French Community of Belgium, the Interuniversity Poles of Attraction Program (P4/21)-Belgian State, and Grant 10NP0201 from the Ministry of Education, Science, Sports and Culture of Japan.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

^¶ To whom all correspondence should be addressed: Unité d'Endocrinologie et Métabolisme, UCL 55.30, Avenue Hippocrate 55, B-1200 Brussels, Belgium. Tel.: 32-2-764-55-29; Fax: 32-2-764-55-32; E-mail: henquin@endo.ucl.ac.be.

---

Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				S. Bao, D. A. Jacobson, M. Wohltmann, A. Bohrer, W. Jin, L. H. Philipson, and J. Turk Glucose homeostasis, insulin secretion, and islet phospholipids in mice that overexpress iPLA2{beta} in pancreatic {beta}-cells and in iPLA2{beta}-null mice Am J Physiol Endocrinol Metab, February 1, 2008; 294(2): E217 - E229. [Abstract] [Full Text] [PDF]

				N. Baroukh, M. A. Ravier, M. K. Loder, E. V. Hill, A. Bounacer, R. Scharfmann, G. A. Rutter, and E. Van Obberghen MicroRNA-124a Regulates Foxa2 Expression and Intracellular Signaling in Pancreatic beta-Cell Lines J. Biol. Chem., July 6, 2007; 282(27): 19575 - 19588. [Abstract] [Full Text] [PDF]

				J. Satrustegui, B. Pardo, and A. del Arco Mitochondrial Transporters as Novel Targets for Intracellular Calcium Signaling Physiol Rev, January 1, 2007; 87(1): 29 - 67. [Abstract] [Full Text] [PDF]

				J. E. Manning Fox, A. V. Gyulkhandanyan, L. S. Satin, and M. B. Wheeler Oscillatory Membrane Potential Response to Glucose in Islet {beta}-Cells: A Comparison of Islet-Cell Electrical Activity in Mouse and Rat Endocrinology, October 1, 2006; 147(10): 4655 - 4663. [Abstract] [Full Text] [PDF]

				M. C. Beauvois, C. Merezak, J.-C. Jonas, M. A. Ravier, J.-C. Henquin, and P. Gilon Glucose-induced mixed [Ca2+]c oscillations in mouse beta-cells are controlled by the membrane potential and the SERCA3 Ca2+-ATPase of the endoplasmic reticulum Am J Physiol Cell Physiol, June 1, 2006; 290(6): C1503 - C1511. [Abstract] [Full Text] [PDF]

				A. Arredouani, Y. Guiot, J.-C. Jonas, L. H. Liu, M. Nenquin, J. A. Pertusa, J. Rahier, J.-F. Rolland, G. E. Shull, M. Stevens, et al. SERCA3 Ablation Does Not Impair Insulin Secretion but Suggests Distinct Roles of Different Sarcoendoplasmic Reticulum Ca2+ Pumps for Ca2+ Homeostasis in Pancreatic {beta}-cells Diabetes, November 1, 2002; 51(11): 3245 - 3253. [Abstract] [Full Text] [PDF]

				L. A. Fahien and M. J. MacDonald The Succinate Mechanism of Insulin Release Diabetes, September 1, 2002; 51(9): 2669 - 2676. [Abstract] [Full Text] [PDF]

				L. J. Brown, R. A. Koza, C. Everett, M. L. Reitman, L. Marshall, L. A. Fahien, L. P. Kozak, and M. J. MacDonald Normal Thyroid Thermogenesis but Reduced Viability and Adiposity in Mice Lacking the Mitochondrial Glycerol Phosphate Dehydrogenase J. Biol. Chem., August 30, 2002; 277(36): 32892 - 32898. [Abstract] [Full Text] [PDF]

				J.-C. Henquin, N. Ishiyama, M. Nenquin, M. A. Ravier, and J.-C. Jonas Signals and Pools Underlying Biphasic Insulin Secretion Diabetes, February 1, 2002; 51(90001): S60 - 67. [Abstract] [Full Text] [PDF]

				R. T. Kennedy, L. M. Kauri, G. M. Dahlgren, and S.-K. Jung Metabolic Oscillations in {beta}-Cells Diabetes, February 1, 2002; 51(90001): S152 - 161. [Abstract] [Full Text] [PDF]

				R. H. Skelly, B. Wicksteed, P. A. Antinozzi, and C. J. Rhodes Glycerol-Stimulated Proinsulin Biosynthesis in Isolated Pancreatic Rat Islets via Adenoviral-Induced Expression of Glycerol Kinase Is Mediated via Mitochondrial Metabolism Diabetes, August 1, 2001; 50(8): 1791 - 1798. [Abstract] [Full Text] [PDF]

				A. Arredouani, J.-C. Henquin, and P. Gilon Contribution of the endoplasmic reticulum to the glucose-induced [Ca2+]c response in mouse pancreatic islets Am J Physiol Endocrinol Metab, May 1, 2002; 282(5): E982 - E991. [Abstract] [Full Text] [PDF]