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) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted 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 Smukler, S. R. Articles by Salapatek, A. M. F. Search for Related Content PubMed PubMed Citation Articles by Smukler, S. R. Articles by Salapatek, A. M. F. Social Bookmarking                What's this?

Exogenous Nitric Oxide and Endogenous Glucose-Stimulated ß-Cell Nitric Oxide Augment Insulin Release

¹ Department of Physiology, University of Toronto, Toronto, Ontario, Canada
² Department of Medicine, University of Toronto, Toronto, Ontario, Canada

The role nitric oxide (NO) plays in physiological insulin secretion has been controversial. Here we present evidence that exogenous NO stimulates insulin secretion, and that endogenous NO production occurs and is involved in the regulation of insulin release. Radioimmunoassay measurement of insulin release and a dynamic assay of exocytosis using the dye FM1-43 demonstrated that three different NO donors—hydroxylamine (HA), sodium nitroprusside, and 3-morpholinosydnonimine (SIN-1)—each stimulated a marked increase in insulin secretion from INS-1 cells. Pharmacological manipulation of the guanylate cyclase/guanosine 3',5'-cyclic monophosphate pathway indicated that this pathway was involved in mediating the effect of the intracellular NO donor, HA, which was used to simulate endogenous NO production. This effect was further characterized as involving membrane depolarization and intracellular Ca²⁺ ([Ca²⁺]_i) elevation. SIN-1 application enhanced glucose-induced [Ca²⁺]_i responses in primary ß-cells and augmented insulin release from islets in a glucose-dependent manner. Real-time monitoring of NO using the NO-sensitive fluorescent dye, diaminofluorescein, was used to provide direct and dynamic imaging of NO generation within living ß-cells. This showed that endogenous NO production could be stimulated by elevation of [Ca²⁺]_i levels and by glucose in both INS-1 and primary rat ß-cells. Scavenging endogenously produced NO-attenuated glucose-stimulated insulin release from INS-1 cells and rat islets. Thus, the results indicated that applied NO is able to exert an insulinotropic effect, and implicated endogenously produced NO in the physiological regulation of insulin release.

CiteULike

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				C. S. Nunemaker, D. G. Buerk, M. Zhang, and L. S. Satin Glucose-induced release of nitric oxide from mouse pancreatic islets as detected with nitric oxide-selective glass microelectrodes Am J Physiol Endocrinol Metab, March 1, 2007; 292(3): E907 - E912. [Abstract] [Full Text] [PDF]

				R. Granata, F. Settanni, L. Biancone, L. Trovato, R. Nano, F. Bertuzzi, S. Destefanis, M. Annunziata, M. Martinetti, F. Catapano, et al. Acylated and Unacylated Ghrelin Promote Proliferation and Inhibit Apoptosis of Pancreatic {beta}-Cells and Human Islets: Involvement of 3',5'-Cyclic Adenosine Monophosphate/Protein Kinase A, Extracellular Signal-Regulated Kinase 1/2, and Phosphatidyl Inositol 3-Kinase/Akt Signaling Endocrinology, February 1, 2007; 148(2): 512 - 529. [Abstract] [Full Text] [PDF]

				H. Mosen, A. Salehi, R. Henningsson, and I. Lundquist Nitric oxide inhibits, and carbon monoxide activates, islet acid {alpha}-glucoside hydrolase activities in parallel with glucose-stimulated insulin secretion. J. Endocrinol., September 1, 2006; 190(3): 681 - 693. [Abstract] [Full Text] [PDF]

				Y. W. Chen, C. F. Huang, K. S. Tsai, R. S. Yang, C. C. Yen, C. Y. Yang, S. Y. Lin-Shiau, and S. H. Liu The Role of Phosphoinositide 3-Kinase/Akt Signaling in Low-Dose Mercury-Induced Mouse Pancreatic {beta}-Cell Dysfunction In Vitro and In Vivo Diabetes, June 1, 2006; 55(6): 1614 - 1624. [Abstract] [Full Text] [PDF]

				E. Bertelli and M. Bendayan Association between Endocrine Pancreas and Ductal System. More than an Epiphenomenon of Endocrine Differentiation and Development? J. Histochem. Cytochem., September 1, 2005; 53(9): 1071 - 1086. [Abstract] [Full Text] [PDF]

				D. Gentilcore, R. Visvanathan, A. Russo, R. Chaikomin, J. E. Stevens, J. M. Wishart, A. Tonkin, M. Horowitz, and K. L. Jones Role of nitric oxide mechanisms in gastric emptying of, and the blood pressure and glycemic responses to, oral glucose in healthy older subjects Am J Physiol Gastrointest Liver Physiol, June 1, 2005; 288(6): G1227 - G1232. [Abstract] [Full Text] [PDF]

				H. Mosen, A. Salehi, P. Alm, R. Henningsson, J. Jimenez-Feltstrom, C.-G. Ostenson, S. Efendic, and I. Lundquist Defective Glucose-Stimulated Insulin Release in the Diabetic Goto-Kakizaki (GK) Rat Coincides with Reduced Activity of the Islet Carbon Monoxide Signaling Pathway Endocrinology, March 1, 2005; 146(3): 1553 - 1558. [Abstract] [Full Text] [PDF]

				J. W. Joseph, V. Koshkin, M. C. Saleh, W. I. Sivitz, C.-Y. Zhang, B. B. Lowell, C. B. Chan, and M. B. Wheeler Free Fatty Acid-induced {beta}-Cell Defects Are Dependent on Uncoupling Protein 2 Expression J. Biol. Chem., December 3, 2004; 279(49): 51049 - 51056. [Abstract] [Full Text] [PDF]

				L. Kapural, S. M. Hayek, M. Stanton-Hicks, and N. Mekhail Decreased Insulin Requirements with Spinal Cord Stimulation in a Patient with Diabetes Anesth. Analg., March 1, 2004; 98(3): 745 - 746. [Abstract] [Full Text] [PDF]

				M. A. Rizzo and D. W. Piston Regulation of {beta} cell glucokinase by S-nitrosylation and association with nitric oxide synthase J. Cell Biol., April 28, 2003; 161(2): 243 - 248. [Abstract] [Full Text] [PDF]