A Neuronal Isoform of Nitric Oxide Synthase Expressed in Pancreatic β-Cells Controls Insulin Secretion
| Autor: | René Gross, Thierry Chardès, Samuel Dietz, M. Manteghetti, Anne-Dominique Lajoix, Christophe Broca, Claes B. Wollheim, Sylvie Peraldi-Roux, M. Roye, Florence Tribillac, Gérard Ribes, Hubbert Reggio |
|---|---|
| Přispěvatelé: | Biologie Intégrative et Virologie des Insectes [Univ. de Montpellier II] (BIVI), Université Montpellier 2 - Sciences et Techniques (UM2)-Institut National de la Recherche Agronomique (INRA) |
| Rok vydání: | 2001 |
| Předmět: |
Male
Miconazole Arginine [SDV]Life Sciences [q-bio] Endocrinology Diabetes and Metabolism Nitric Oxide Synthase Type I Mitochondrion Subcellular Fractions/enzymology Cell Membrane/drug effects/physiology chemistry.chemical_compound Insulin Secretion Insulin Tissue Distribution Clotrimazole ddc:616 Cytochrome c Drug Synergism Nitroprusside/pharmacology NOS Electrophysiology Nitric oxide synthase medicine.anatomical_structure Sodium nitroprusside CONTROLE Subcellular Fractions medicine.drug Nitroprusside Gene isoform medicine.medical_specialty Nitric Oxide Synthase/antagonists & inhibitors/genetics/metabolism Molecular Sequence Data Clotrimazole/pharmacology Biology Nitric oxide Islets of Langerhans Glucose/administration & dosage/pharmacology Internal medicine Internal Medicine medicine Animals Succinates/pharmacology Rats Wistar Insulin/secretion Base Sequence Dose-Response Relationship Drug Pancreatic islets Islets of Langerhans/drug effects/metabolism/physiology Cell Membrane Succinates Base Sequence/genetics Miconazole/pharmacology Rats Glucose Endocrinology nervous system chemistry biology.protein Nitric Oxide Synthase Arginine/pharmacology |
| Zdroj: | Diabetes, Vol. 50, No 6 (2001) pp. 1311-23 Diabetes Diabetes, American Diabetes Association, 2001, 50, pp.1311-1323 |
| ISSN: | 1939-327X 0012-1797 |
| DOI: | 10.2337/diabetes.50.6.1311 |
| Popis: | Evidence is presented showing that a neuronal isoform of nitric oxide synthase (NOS) is expressed in rat pancreatic islets and INS-1 cells. Sequencing of the coding region indicated a 99.8% homology with rat neuronal NOS (nNOS) with four mutations, three of them resulting in modifications of the amino acid sequence. Double-immunofluorescence studies demonstrated the presence of nNOS in insulin-secreting beta-cells. Electron microscopy studies showed that nNOS was mainly localized in insulin secretory granules and to a lesser extent in the mitochondria and the nucleus. We also studied the mechanism involved in the dysfunction of the beta-cell response to arginine and glucose after nNOS blockade with N(G)-nitro-L-arginine methyl ester. Our data show that miconazole, an inhibitor of nNOS cytochrome c reductase activity, either alone for the experiments with arginine or combined with sodium nitroprusside for glucose, is able to restore normal secretory patterns in response to the two secretagogues. Furthermore, these results were corroborated by the demonstration of a direct enzyme-substrate interaction between nNOS and cytochrome c, which is strongly reinforced in the presence of the NOS inhibitor. Thus, we provide immunochemical and pharmacological evidence that beta-cell nNOS exerts, like brain nNOS, two catalytic activities: a nitric oxide production and an NOS nonoxidating reductase activity, both of which are essential for normal beta-cell function. In conclusion, we suggest that an imbalance between these activities might be implicated in beta-cell dysregulation involved in certain pathological hyperinsulinic states. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|