Diabetes
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Diabetes 55:3279-3288, 2006
DOI: 10.2337/db06-0257
© 2006 by the American Diabetes Association
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Lajoix, A.-D.
Right arrow Articles by Gross, R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lajoix, A.-D.
Right arrow Articles by Gross, R.
Social Bookmarking
Add to CiteULike   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Protein Inhibitor of Neuronal Nitric Oxide Synthase (PIN) Is a New Regulator of Glucose-Induced Insulin Secretion

Anne-Dominique Lajoix1, Stéphanie Badiou2, Sylvie Péraldi-Roux1, Thierry Chardès1, Samuel Dietz3, Cindy Aknin4, Florence Tribillac5, Pierre Petit1, and René Gross1

1 Centre National de la Recherche Scientifique, Unité Mixte de Recherche (CNRS UMR) 5160, Center for Pharmacology and Health Biotechnology, Montpellier, France
2 Department of Biochemistry, University Hospital, Montpellier, France
3 INNODIA SAS, Montpellier, France
4 CNRS UMR 5203, Institut de Génomique Fonctionnelle, Montpellier, France
5 Centre Régional d’Imagerie Cellulaire, Institut Universitaire de Recherche Clinique, Montpellier, France

Address correspondence and reprint requests to René Gross, CNRS UMR 5160, Faculté de Pharmacie, 15 Ave. Charles Flahault, BP 14491, 34093 Montpellier Cedex 5, France. E-mail: rene.gross{at}univ-montp1.fr

Abbreviations: eNOS, endothelial nitric oxide synthase; FITC, fluorescein isothiocyanate; iNOS, cytokine-inducible nitric oxide synthase; L-NAME, N{omega}-nitro-L-arginine methyl ester; nNOS, neuronal nitric oxide synthase; NOS, nitric oxide synthase; PIN, protein inhibitor of nNOS; SNP, sodium nitroprusside

We previously showed that pancreatic ß-cells express neuronal nitric oxide synthase (nNOS) that controls insulin secretion through two catalytic activities: nitric oxide (NO) production and cytochrome c reductase activity. We now provide evidence that the endogenous protein inhibitor of nNOS (PIN) is expressed in rat pancreatic islets and INS-1 cells. Double-immunofluorescence studies showed a colocalization of PIN with both nNOS and myosin Va in insulin-secreting ß-cells. Electron microscopy studies confirmed that PIN is mainly associated with insulin secretory granules and colocated with nNOS in the latter. In addition, PIN overexpression in INS-1 cells enhanced glucose-induced insulin secretion, which is only partly reversed by addition of an NO donor, sodium nitroprusside (SNP), and unaffected by the inhibitor of cytochrome c reductase activity, miconazole. In contrast, the pharmacological inhibitor of nNOS, N{omega}-nitro-L-arginine methyl ester, amplified glucose-induced insulin secretion, an effect insensitive to SNP but completely normalized by the addition of miconazole. Thus, PIN insulinotropic effect could be related to its colocalization with the actin-based molecular motor myosin Va and as such be implicated in the physiological regulation of glucose-induced insulin secretion at the level of the exocytotic machinery.


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




HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Diabetes Diabetes Care Clinical Diabetes Diabetes Spectrum
Copyright © 2006 by the American Diabetes Association.