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

J. Biol. Chem., Vol. 279, Issue 31, 32316-32324, July 30, 2004

This Article Full Text Full Text (PDF) All Versions of this Article: 279/31/32316    most recent M402076200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted 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 Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Nenquin, M. Articles by Henquin, J.-C. Search for Related Content PubMed PubMed Citation Articles by Nenquin, M. Articles by Henquin, J.-C. Social Bookmarking                      What's this?

Both Triggering and Amplifying Pathways Contribute to Fuel-induced Insulin Secretion in the Absence of Sulfonylurea Receptor-1 in Pancreatic -Cells^*

Myriam Nenquin, Andras Szollosi, Lydia Aguilar-Bryan¶, Joseph Bryan||, and Jean-Claude Henquin**

From the Unité d'Endocrinologie et Métabolisme, University of Louvain Faculty of Medicine UCL 55.30, Ave. Hippocrate 55, B-1200 Brussels, Belgium and the Departments of ^¶Medicine and ^||Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030

In normal -cells glucose induces insulin secretion by activating both a triggering pathway (closure of K_ATP channels, depolarization, and rise in cytosolic [Ca²⁺]_i) and an amplifying pathway (augmentation of Ca²⁺ efficacy on exocytosis). It is unclear if and how nutrients can regulate insulin secretion by -cells lacking K_ATP channels (Sur1 knockout mice). We compared glucose- and amino acid-induced insulin secretion and [Ca²⁺]_i changes in control and Sur1KO islets. In 1 mM glucose (non-stimulatory for controls), the triggering signal [Ca²⁺]_i was high (loss of regulation) and insulin secretion was stimulated in Sur1KO islets. This "basal" secretion was decreased or increased by imposed changes in [Ca²⁺]_i and was dependent on ATP production, indicating that both triggering and amplifying signals are involved. High glucose stimulated insulin secretion in Sur1KO islets, by an unsuspected, transient increase in [Ca²⁺]_i and a sustained activation of the amplifying pathway. Unlike controls, Sur1KO islets were insensitive to diazoxide and tolbutamide, which rules out effects of either drug at sites other than K_ATP channels. Amino acids potently increased insulin secretion by Sur1KO islets through both a further electrogenic rise in [Ca²⁺]_i and a metabolism-dependent activation of the amplifying pathway. After sulfonylurea blockade of their K_ATP channels, control islets qualitatively behaved like Sur1KO islets, but their insulin secretion rate was consistently lower for a similar or even higher [Ca²⁺]_i. In conclusion, fuel secretagogues can control insulin secretion in -cells without K_ATP channels, partly by an unsuspected influence on the triggering [Ca²⁺]_i signal and mainly by the modulation of a very effective amplifying pathway.

Received for publication, February 25, 2004 , and in revised form, April 23, 2004.

^* This work was supported by Grant 3.4552.98 from the Fonds de la Recherche Scientifique Médicale (Brussels), by Grant ARC 00/05-260 from the General Direction of Scientific Research of the French Community of Belgium, by the Interuniversity Attraction Poles Programme (Grant PAI 5/17) Belgian Science Policy, and by Grants NIH-DK52771 and NIH-DK57671 from the National Institutes of Health. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Both authors contributed equally to this work.

^** To whom correspondence should be addressed. Tel.: 32-2-764-5529; Fax: 32-2-764-5532; E-mail: henquin{at}endo.ucl.ac.be.

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

This article has been cited by other articles:

				M. A. Ravier, M. Nenquin, T. Miki, S. Seino, and J.-C. Henquin Glucose Controls Cytosolic Ca2+ and Insulin Secretion in Mouse Islets Lacking Adenosine Triphosphate-Sensitive K+ Channels Owing to a Knockout of the Pore-Forming Subunit Kir6.2 Endocrinology, January 1, 2009; 150(1): 33 - 45. [Abstract] [Full Text] [PDF]

				M. V. Jensen, J. W. Joseph, S. M. Ronnebaum, S. C. Burgess, A. D. Sherry, and C. B. Newgard Metabolic cycling in control of glucose-stimulated insulin secretion Am J Physiol Endocrinol Metab, December 1, 2008; 295(6): E1287 - E1297. [Abstract] [Full Text] [PDF]

				S. M. Ronnebaum, J. W. Joseph, O. Ilkayeva, S. C. Burgess, D. Lu, T. C. Becker, A. D. Sherry, and C. B. Newgard Chronic Suppression of Acetyl-CoA Carboxylase 1 in {beta}-Cells Impairs Insulin Secretion via Inhibition of Glucose Rather Than Lipid Metabolism J. Biol. Chem., May 23, 2008; 283(21): 14248 - 14256. [Abstract] [Full Text] [PDF]

				J. W. Joseph, M. L. Odegaard, S. M. Ronnebaum, S. C. Burgess, J. Muehlbauer, A. D. Sherry, and C. B. Newgard Normal Flux through ATP-Citrate Lyase or Fatty Acid Synthase Is Not Required for Glucose-stimulated Insulin Secretion J. Biol. Chem., October 26, 2007; 282(43): 31592 - 31600. [Abstract] [Full Text] [PDF]

				B. Malester, X. Tong, I. Ghiu, A. Kontogeorgis, D. E. Gutstein, J. Xu, K. D. Hendricks-Munoz, and W. A. Coetzee Transgenic expression of a dominant negative KATP channel subunit in the mouse endothelium: effects on coronary flow and endothelin-1 secretion FASEB J, July 1, 2007; 21(9): 2162 - 2172. [Abstract] [Full Text] [PDF]

				X. Geng, L. Li, R. Bottino, A. N. Balamurugan, S. Bertera, E. Densmore, A. Su, Y. Chang, M. Trucco, and P. Drain Antidiabetic sulfonylurea stimulates insulin secretion independently of plasma membrane KATP channels Am J Physiol Endocrinol Metab, July 1, 2007; 293(1): E293 - E301. [Abstract] [Full Text] [PDF]

				A. Szollosi, M. Nenquin, and J.-C. Henquin Overnight Culture Unmasks Glucose-induced Insulin Secretion in Mouse Islets Lacking ATP-sensitive K+ Channels by Improving the Triggering Ca2+ Signal J. Biol. Chem., May 18, 2007; 282(20): 14768 - 14776. [Abstract] [Full Text] [PDF]

				O. T. Hardy, H. E. Hohmeier, T. C. Becker, E. Manduchi, N. M. Doliba, R. K. Gupta, P. White, C. J. Stoeckert Jr, F. M. Matschinsky, C. B. Newgard, et al. Functional Genomics of the {beta}-Cell: Short-Chain 3-Hydroxyacyl-Coenzyme A Dehydrogenase Regulates Insulin Secretion Independent of K+ Currents Mol. Endocrinol., March 1, 2007; 21(3): 765 - 773. [Abstract] [Full Text] [PDF]

				C. Miele, G. A. Raciti, A. Cassese, C. Romano, F. Giacco, F. Oriente, F. Paturzo, F. Andreozzi, A. Zabatta, G. Troncone, et al. PED/PEA-15 Regulates Glucose-Induced Insulin Secretion by Restraining Potassium Channel Expression in Pancreatic {beta}-Cells Diabetes, March 1, 2007; 56(3): 622 - 633. [Abstract] [Full Text] [PDF]

				A. Szollosi, M. Nenquin, L. Aguilar-Bryan, J. Bryan, and J.-C. Henquin Glucose Stimulates Ca2+ Influx and Insulin Secretion in 2-Week-old beta-Cells Lacking ATP-sensitive K+ Channels J. Biol. Chem., January 19, 2007; 282(3): 1747 - 1756. [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]

				A. Hambrock, C. B. de Oliveira Franz, S. Hiller, and H. Osswald Glibenclamide-Induced Apoptosis Is Specifically Enhanced by Expression of the Sulfonylurea Receptor Isoform SUR1 but Not by Expression of SUR2B or the Mutant SUR1(M1289T) J. Pharmacol. Exp. Ther., March 1, 2006; 316(3): 1031 - 1037. [Abstract] [Full Text] [PDF]

				A. Munoz, M. Hu, K. Hussain, J. Bryan, L. Aguilar-Bryan, and A. S. Rajan Regulation of Glucagon Secretion at Low Glucose Concentrations: Evidence for Adenosine Triphosphate-Sensitive Potassium Channel Involvement Endocrinology, December 1, 2005; 146(12): 5514 - 5521. [Abstract] [Full Text] [PDF]

				M. S. Remedi, J. C. Koster, B. L. Patton, and C. G. Nichols ATP-Sensitive K+ Channel Signaling in Glucokinase-Deficient Diabetes Diabetes, October 1, 2005; 54(10): 2925 - 2931. [Abstract] [Full Text] [PDF]

				M. S. Remedi, Joseph. C. Koster, K. Markova, S. Seino, T. Miki, B. L. Patton, M. L. McDaniel, and C. G. Nichols Diet-Induced Glucose Intolerance in Mice With Decreased {beta}-Cell ATP-Sensitive K+ Channels Diabetes, December 1, 2004; 53(12): 3159 - 3167. [Abstract] [Full Text] [PDF]

				J.-C. Henquin Pathways in Beta-Cell Stimulus-Secretion Coupling as Targets for Therapeutic Insulin Secretagogues Diabetes, December 1, 2004; 53(suppl_3): S48 - S58. [Abstract] [Full Text] [PDF]