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Mechanisms involved in the effect of nitric oxide synthase inhibition on L-arginine-induced insulin secretion
| Content Provider | Scilit |
|---|---|
| Author | Gross, R. Roye, M. Manteghetti, M. Broca, C. Hillaire-Buys, D. Masiello, P. Ribes, G. |
| Copyright Year | 1997 |
| Description | Journal: British Journal of Pharmacology |
| Abstract | 1 A constitutive nitric oxide synthase (NOSc) pathway negatively controls L‐arginine‐stimulated insulin release by pancreatic β cells. We investigated the effect of glucose on this mechanism and whether it could be accounted for by nitric oxide production. 2 NOSc was inhibited by $N^{∞}$‐nitro‐L‐arginine methyl ester (l‐NAME), and sodium nitroprusside (SNP) was used as a palliative NO donor to test whether the effects of L‐NAME resulted from decreased NO production. 3 In the rat isolated perfused pancreas, L‐NAME (5 mM) strongly potentiated L‐arginine (5 mM)‐induced insulin secretion at 5 mM glucose, but L‐arginine and L‐NAME exerted only additive effects at 8.3 mM glucose. At 11 mM glucose, L‐NAME significantly inhibited L‐arginine‐induced insulin secretion. Similar data were obtained in rat isolated islets. 4 At high concentrations (3 and 300 μm), SNP increased the potentiation of arginine‐induced insulin output by L‐NAME, but not at lower concentrations (3 or 30 nM). 5 L‐Arginine (5 mM) and L‐ornithine (5 mM) in the presence of 5 mM glucose induced monophasic β cell responses which were both significantly reduced by SNP at 3 nM but not at 30 nM; in contrast, the L‐ornithine effect was significantly increased by SNP at 3 μm. 6 Simultaneous treatment with L‐ornithine and L‐arginine provoked a biphasic insulin response. 7 At 5 mM glucose, L‐NAME (5 mM) did not affect the L‐ornithine secretory effect, but the amino acid strongly potentiated the alteration by L‐NAME of L‐arginine‐induced insulin secretion. 8 L‐Citrulline (5 mM) significantly reduced the second phase of the insulin response to L‐NAME (5 mM) + L‐arginine (5 mM) and to L‐NAME + L‐arginine + SNP 3 μm. 9 The intermediate in NO biosynthesis, $N^{G}$‐hydroxy‐L‐arginine (150–300 μm) strongly counteracted the potentiation by L‐NAME of the secretory effect of L‐arginine at 5 mM glucose. 10 We conclude that the potentiation of L‐arginine‐induced insulin secretion resulting from the blockade of NOSc activity in the presence of a basal glucose concentration (1) is strongly modulated by higher glucose concentrations, (2) is not due to decreased NO production but (3) is probably accounted for by decreased levels of $N^{G}$‐hydroxy‐L‐arginine or L‐citrulline, resulting in the attenuation of an inhibitory effect on arginase activity. |
| Related Links | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1564475/pdf |
| Ending Page | 501 |
| Page Count | 7 |
| Starting Page | 495 |
| e-ISSN | 14765381 |
| DOI | 10.1038/sj.bjp.0700911 |
| Journal | British Journal of Pharmacology |
| Issue Number | 3 |
| Volume Number | 120 |
| Language | English |
| Publisher | Wiley-Blackwell |
| Publisher Date | 1997-01-01 |
| Access Restriction | Open |
| Subject Keyword | Journal: British Journal of Pharmacology Insulin Secretion Nitric Oxide Synthase Inhibitor Nω-nitro-l-arginine Methyl Ester Ng-hydroxy-l-arginine Sodium Nitroprusside |
| Content Type | Text |
| Resource Type | Article |
