Nitric Oxide and Arginine-Evoked Insulin Secretion

Thouvenot, Vincent

doi:10.1126/science.1455235

Cited by 46 publications

(20 citation statements)

References 9 publications

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“…Very recently, evidence has been obtained direct depolarizing effect of the cationic amino acid. Since for the occurrence of NO synthase activity in both endocrine NO synthase inhibition increased L-arginine-induced insulin cells and nerves of the islets of Langerhans (Schmidt et al, release (Panagiotidis et al, 1992) we suggested that the 1992; Vincent, 1992;Panagiotidis et al, 1992;Corbett et al, stimulating effect of L-arginine was in part counteracted by 1993). Previous data (Laychock et al, 1991;Schmidt et al, the concomitant production of NO.…”

Section: Introductionmentioning

confidence: 86%

Influence of nitric oxide synthase inhibition, nitric oxide and hydroperoxide on insulin release induced by various secretagogues

Panagiotidis

Åkesson

Rydell

et al. 1995

British J Pharmacology

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1 Recent studies have suggested that the generation of nitric oxide (NO) and hydrogen peroxide (H202) by islet NO synthase and monoamine oxidase, respectively, may have a regulatory influence on insulin secretory processes. We have investigated the pattern of insulin release from isolated islets of Langerhans in the presence of various pharmacological agents known to perturb the intracellular levels of NO and the oxidation state of SH-groups.2 The NO synthase inhibitor, N0-nitro-L-arginine methyl ester (L-NAME) dose-dependently increased L-arginine-induced insulin release. D-Arginine did not influence L-arginine-induced insulin secretion.However, D-NAME which reportedly has no inhibitory action on NO synthase, modestly increased L-arginine-induced insulin release, but was less effective than L-NAME. High concentrations (10 mM) of D-arginine as well as L-NAME and D-NAME could enhance basal insulin release. 3 The intracellular NO donor, hydroxylamine, dose-dependently inhibited insulin secretion induced by L-arginine and L-arginine + L-NAME.4 Glucose-induced insulin release was increased by NO synthase inhibition (L-NAME) and inhibited by the intracellular NO donor, hydroxylamine. Sydnonimine-I (SIN-1), an extracellular donor of NO and superoxide, induced a modest suppression of glucose-stimulated insulin release. SIN-1 did not influence insulin secretion induced by L-arginine or the adenylate cyclase activator, forskolin. L-arginine or tert-butylhydroperoxide at 3 or 300 gM but was markedly increased (14 fold) by a high hydroxylamine concentration (300 gM). In contrast, islet adenosine 3':5'-cyclic monophosphate (cyclic AMP) content was increased (3 fold) by L-arginine (10 mM) and (2 fold) by tert-butylhydroperoxide (300 gM).7 Our results strongly suggest that NO is a negative modulator of insulin release induced by the nutrient secretagogues L-arginine and glucose. This effect is probably not mediated to any major extent by the guanylate cyclase-cyclic GMP system but may rather be exerted by the S-nitrosylation of critical thiol groups involved in the secretory process. Similarly the inhibitory effect of tert-butylhydroperoxide is likely to be elicited through affecting critical thiol groups. The mechanism underlying the secretionpromoting action of tert-butylhydroperoxide on IBMX-induced insulin release is probably linked to intracellular Ca2'-perturbations affecting exocytosis.8 Taken together with previous data the present results suggest that islet production of low physiological levels of free radicals such as NO and H202 may serve as important modulators of insulin secretory processes.

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Section: Introductionmentioning

confidence: 86%

Influence of nitric oxide synthase inhibition, nitric oxide and hydroperoxide on insulin release induced by various secretagogues

Panagiotidis

Åkesson

Rydell

et al. 1995

British J Pharmacology

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“…Some investigators described NOS-immunoreactivity and/or NADPH-diaphorase staining in the majority of rat and mouse islet cells [6,12], whereas others failed to detect NOS-immunoreactivity in human and rat islets [13±15]. Apart from the important influence of the fixation procedures used [14,15] and species differences, the existence of local isoforms of NOS may account for the observed discrepancies [15].…”

Section: Discussionmentioning

confidence: 99%

The early phase of glucose-stimulated insulin secretion requires nitric oxide

Spinas¹,

Laffranchi²,

Francoys³

et al. 1998

Diabetologia

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Nitric oxide (nitrogen monoxide; NO) is an important messenger molecule in various cell types, e. g. endothelial cells [1], neurons [2], or T lymphocytes [3]. However, when produced in large amounts and over prolonged periods of time, e. g. by macrophages [4], NO is cytotoxic.In pancreatic beta cells NO produced upon activation of the inducible isoform of NO synthase by cytokines causes beta-cell destruction [5]. There is also evidence that NO could function as signal transmitter in beta cells. However, results obtained in pursuit of a possible involvement of NO in the signalling pathway of insulin secretion are controversial. Some investigations provided evidence that NO, presumably produced by a calcium/calmodulin-dependent constitutive NO synthase (NOS), participates in the signal transduction pathway mediating insulin secretion [6], and that L-arginine-derived NO mediates insulin secretion via stimulation of guanylate cyclase and cGMP formation [7]. Others found no evidence for endogenously produced NO being involved in the initiation of secretagogue-induced insulin release [8] or reported that L-arginine-derived NO may even inhibit insulin release [9].Recently, Willmott et al. [10] showed that beta cells preloaded with tryptamine, which accumulates in insulin-containing granules and is co-secreted with insulin, respond to NO by mobilizing Ca 2+ from the endoplasmic reticulum accompanied by a release of tryptamine from the cells. These data corroborate our previous finding that exogenously added NO Diabetologia (1998) Summary Nitric oxide (nitrogen monoxide, NO) acts as a signal transducer in a variety of cells. In the present study rat pancreatic islets were perifused with physiologically relevant glucose concentrations in the presence or absence of various NO-modulating agents. Perifusion in the presence of 0.1±1 mmol/l of the NO synthase inhibitor, N G -monomethyl-L-arginine or of 10 mmol/l of the NO-scavenger, 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (carboxy-PTIO), resulted in an inhibition of the early phase of glucose-stimulated insulin secretion by 60±65 % and 46 %, respectively. Light-and electron-microscopic studies revealed that pancreatic islets constitutively express NO-synthase in alpha and delta cells, where it is confined to the secretory granules. Therefore, these data indicate that NO may be important in the signal transduction pathway of the early phase of glucose-stimulated insulin secretion.[ Diabetologia (1998) 41: 292±299]

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“…Thus L-arginine-derived NO has been suggested not to be involved in L-arginine stimulation of insulin secretion (6,14,15), to enhance L-arginine stimulation of insulin secretion (16,17), or to inhibit Larginine stimulation of insulin secretion from pancreatic b-cells (18)(19)(20). In accordance with a possible significance of NO in L-arginine stimulation of insulin secretion, islets have been found to express the constitutive, Ca 2+ /calmodulin-dependent nitric oxide synthase (cNOS), which may exhibit glucose-sensitive NO synthesis in the presence of L-arginine (16,20).…”

Section: Introductionmentioning

confidence: 99%

L-arginine stimulation of glucose-induced insulin secretion through membrane depolarization and independent of nitric oxide

Thams

Capito²

1999

European Journal of Endocrinology

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The mechanism of L-arginine stimulation of glucose-induced insulin secretion from mouse pancreatic islets was studied. At 16.7 mmol/l glucose, L-arginine (10 mmol/l) potentiated both phases 1 and 2 of glucose-induced insulin secretion. This potentiation of glucose-induced insulin secretion was mimicked by the membrane depolarizing agents tetraethylammonium (TEA, 20 mmol/l) and K + (60 mmol/l), which at 16.7 mmol/l glucose obliterated L-arginine (10 mmol/l) modulation of insulin secretion. Thus L-arginine may potentiate glucose-induced insulin secretion by stimulation of membrane depolarization. At 3.3 mmol/l glucose, L-arginine (10 mmol/l) failed to stimulate insulin secretion. In accordance with membrane depolarization by the electrogenic transport of L-arginine, however, L-arginine (10 mmol/l) stimulation of insulin secretion was enabled by the K + channel inhibitor TEA (20 mmol/l), which potentiates membrane depolarization by L-arginine. Furthermore, Larginine (10 mmol/l) stimulation of insulin secretion was permitted by forskolin (10 mmol/l) or tetradecanoylphorbol 13-acetate (0.16 mmol/l), which, by activation of protein kinases A and C respectively sensitize the exocytotic machinery to L-arginine-induced Ca 2+ influx. Thus glucose may sensitize L-arginine stimulation of insulin secretion by potentiation of membrane depolarization and by activation of protein kinase A or protein kinase C. Finally, L-arginine stimulation of glucose-induced insulin secretion was mimicked by N G -nitro-L-arginine methyl ester (10 mmol/l), which stimulates membrane depolarization but inhibits nitric oxide synthase, suggesting that L-arginine-derived nitric oxide neither inhibits nor stimulates insulin secretion. In conclusion, it is suggested that L-arginine potentiation of glucose-induced insulin secretion occurs independently of nitric oxide, but is mediated by membrane depolarization, which stimulates insulin secretion through protein kinase A-and Csensitive mechanisms.

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Nitric Oxide and Arginine-Evoked Insulin Secretion

Cited by 46 publications

References 9 publications

Influence of nitric oxide synthase inhibition, nitric oxide and hydroperoxide on insulin release induced by various secretagogues

Influence of nitric oxide synthase inhibition, nitric oxide and hydroperoxide on insulin release induced by various secretagogues

The early phase of glucose-stimulated insulin secretion requires nitric oxide

L-arginine stimulation of glucose-induced insulin secretion through membrane depolarization and independent of nitric oxide

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