Nitric oxide-cyclic GMP system potentiates glucose-induced rise in cytosolic Ca2+ concentration in rat pancreatic β-cells

Matsuura, Noriko; Ishikawa, Tomohisa; Abe, Shinichi; Yuyama, Hironori; Sugino, Fumi; Ishii, Kunio; Nakayama, Koichi

doi:10.1016/s0024-3205(99)00392-6

Cited by 20 publications

(24 citation statements)

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“…This disparity may be attributable to differences in experimental design, such as the time frame of NO stimulation (i.e., minutes or an hour) or whether a phosphodiesterase inhibitor was included. Our finding that NO is able to induce an elevation of ␤-cell [Ca 2ϩ ] i is in agreement with previous studies in rat ␤-cells and cell lines (7,21,22,47 tionality, we used the NO-sensitive fluorescent dye, Daf2 (38), to image NO production in living ␤-cells. To our knowledge, this is the first study to use Daf2 to directly monitor and provide real-time, dynamic visualization of endogenous NO production or generation from exogenous donors in living insulin-secreting cells.…”

Section: Discussionsupporting

confidence: 91%

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

et al. 2002

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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 T he endogenous synthesis of nitric oxide (NO) from L-arginine (L-arg) has been shown to play a critical role in a wide variety of physiological functions including neurotransmission, vascular tone, platelet aggregation, immunological reactions, penile erection, and endocrine and exocrine function (1). Cellular NO is synthesized by a family of NO synthase (NOS) enzymes, comprised of constitutively expressed, Ca 2ϩ / calmodulin-dependent neuronal NOS (nNOS) and endothelial NOS (eNOS), and a Ca 2ϩ /calmodulin-independent inducibly expressed NOS (iNOS) (2).Pancreatic ␤-cells are able to express the iNOS enzyme in response to inflammatory stimuli, leading to high cytotoxic levels of NO production, which appear to be involved in ␤-cell damage, dysfunction, and death and the pathogenesis of type 1 diabetes (3,4). The presence of a constitutive NOS (cNOS) enzyme in ␤-cells is substantiated by considerable evidence, including biochemical, histochemical, immunohistochemical, immunofluorescence, RT-PCR, and protein immunoblot analyses (5-11). Given that the amino acid NO precursor L-arg has long been known to stimulate insulin release (12), it has been postulated that a low level of NO produced from the ␤-cell cNOS isoform functions in the regulation of insulin release. However, several reports in which cNOS activity was manipulated or exogenous NO was applied have yielded seemingly conflicting results. NOS inhibition has been reported to produce an inhibitory effect (5,13-15), a stimulatory effect (6,9,16 -18), and no effect at all (19,20) on insulin release. Similarly, exogenously applied NO has been reported to exert a stimulatory (5,13,14,21,22) and an inhibitory effect (6,18,23-27) on insulin release. These discrepant data may be the result of variations in the specifics of the experimental conditions, including differences in the agents used (e.g., NOS substrate, NOS inhibitors, NO donors), the concentration of these agents, whether other stimulatory pathways were activated concurrently (e.g., with glucose), the experimental model used (e.g., ␤-cell line, islets, pancreas), and the species. These critical differences may result in d...

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Section: Discussionsupporting

confidence: 91%

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

et al. 2002

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“…More recent studies suggest that cyclic GMP could mediate the effects of low concentrations of nitric oxide in augmenting glucose-induced Ca 2+ oscillations and insulin secretion in rat-isolated beta cells [48,49,50]. 8-bromoguanosine-cyclic GMP was found to augment glucose-induced Ca 2+ oscillations in mouse islets and to inhibit K ATP channel activity in mouse-intact beta cells [51].…”

Section: Cyclic Gmpmentioning

confidence: 99%

Cyclic nucleotide phosphodiesterases in pancreatic islets

Pyne

Furman

2003

Diabetologia

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Cyclic nucleotide phosphodiesterases (PDEs) comprise a family of enzymes (PDE1-PDE11) which hydrolyse cyclic AMP and cyclic GMP to their biologically inactive 5′ derivatives. Cyclic AMP is an important physiological amplifier of glucose-induced insulin secretion. As PDEs are the only known mechanism for inactivating cyclic nucleotides, it is important to characterise the PDEs present in the pancreatic islet beta cells. Several studies have shown pancreatic islets or beta cells to contain PDE1C, PDE3B and PDE4, with some evidence for PDE10A. Most evidence suggests that PDE3B is the most important in relation to the regulation of insulin release, although PDE1C could have a role. PDE3-selective inhibitors augment glucose-induced insulin secretion. In contrast, activation of beta-cell PDE3B could mediate the inhibitory effect of IGF-1 and leptin on insulin secretion. In vivo, although PDE3 inhibitors augment glucose-induced insulin secretion, concomitant inhibition of PDE3B in liver and adipose tissue induce insulin resistance and PDE3 inhibitors do not induce hypoglycaemia. The development of PDE3 inhibitors as anti-diabetic agents would require differentiation between PDE3B in the beta cell and that in hepatocytes and adipocytes. Through their effects in regulating beta-cell cyclic nucleotide concentrations, PDEs could modulate beta-cell growth, differentiation and survival; some work has shown that selective inhibition of PDE4 prevents diabetes in NOD mice and that selective PDE3 inhibition blocks cytokine-induced nitric oxide production in islet cells. Further work is required to understand the mechanism of regulation and role of the various PDEs in islet-cell function and to validate them as targets for drugs to treat and prevent diabetes. [Diabetologia (2003[Diabetologia ( ) 46:1179[Diabetologia ( -1189

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“…Control studies performed with each vehicle alone showed that there were no apparent effects of each vehicle at the concentrations used in any of the protocols. A saturated solution of NO, the concentration of which was estimated to be 2 mM, was made by applying NO gas to distilled, degassed water according to the method described previously (29) and kept on ice. Aqueous NO solution at 2 or 20 M was made by diluting the saturated solution with the HK solution just before its application.…”

Section: Drugsmentioning

confidence: 99%

“…Measurements of [Ca 2ϩ ]c. Pancreatic ␤-cells were isolated from male Wistar rats (9-12 wk old, 200-300 g; SLC, Hamamatsu, Japan) by the collagenase digestion technique as described previously (29). The dispersed ␤-cells were plated on coverslips and cultured for 1 day in RPMI-1640 medium (Sigma) supplemented with 10% fetal bovine serum, 100 g/ml streptomycin, and 100 U/ml penicillin.…”

Section: Drugsmentioning

confidence: 99%

“…Several studies have shown that a rise in the cGMP level in ␤-cells stimulates insulin secretion (15,26). We previously reported that an aqueous NO solution as well as 8-bromo-cGMP elevates the cytosolic Ca 2ϩ concentration ([Ca 2ϩ ] c ) at 7.0 mM glucose in isolated rat ␤-cells (29). Thus NO is predicted to facilitate glucose-induced insulin secretion via the stimulation of cGMP formation.…”

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confidence: 94%

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Dual effect of nitric oxide on cytosolic Ca²⁺concentration and insulin secretion in rat pancreatic β-cells

Kaneko

Ishikawa

Amano

et al. 2003

American Journal of Physiology-Cell Physiology

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Kaneko, Yukiko, Tomohisa Ishikawa, Satoshi Amano, and Koichi Nakayama. Dual effect of nitric oxide on cytosolic Ca 2ϩ concentration and insulin secretion in rat pancreatic ␤-cells. Am J Physiol Cell Physiol 284: C1215-C1222, 2003. First published January 15, 2003 10.1152/ajpcell.00223.2002In isolated rat pancreatic ␤-cells, the nitric oxide (NO) donor NOC-7 at 1 M reduced the amplitude of the oscillations of cytosolic Ca 2ϩ concentration ([Ca 2ϩ ]c) induced by 11.1 mM glucose, and at 10 M terminated them. In the presence of N G -nitro-L-arginine (L-NNA), however, NOC-7 at 0.5 and 1 M increased the amplitude of the [Ca 2ϩ ]c oscillations, although the NO donor at 10 M still suppressed them. Aqueous NO solution also had a dual effect on the [Ca 2ϩ ]c oscillations. The soluble guanylate cyclase inhibitor LY-83583 and the cGMP-dependent protein kinase inhibitor KT5823 inhibited the stimulatory effect of NO, and 8-bromo-cGMP increased the amplitude of the [Ca 2ϩ ]c oscillations. Patch-clamp analyses in the perforated configuration showed that 8-bromo-cGMP inhibited whole cell ATP-sensitive K ϩ currents in the isolated rat pancreatic ␤-cells, suggesting that the inhibition by cGMP of ATP-sensitive K ϩ channels is, at least in part, responsible for the stimulatory effect of NO on the [Ca 2ϩ ]c oscillations. In the presence of L-NNA, the glucose-induced insulin secretion from isolated islets was facilitated by 0.5 M NOC-7, whereas it was suppressed by 10 M NOC-7. These results suggest that NO facilitates glucose-induced [Ca 2ϩ ]c oscillations of ␤-cells and insulin secretion at low concentrations, which effects are mediated by cGMP, whereas NO inhibits them in a cGMP-independent manner at high concentrations.islets of Langerhans; calcium oscillations; guanosine 3Ј,5Ј-cyclic monophosphate; NOC-7; glucose NITRIC OXIDE (NO) produced from L-arginine by NO synthase (NOS) is an important regulator of various physiological and pathological functions in various types of cells. In pancreatic islets, a large amount of NO generated by inducible NOS (iNOS) has been postulated to be involved in ␤-cell degeneration in the process of insulin-dependent diabetes mellitus (1,6,22). On the other hand, recent immunostaining studies clearly demonstrated the presence of constitutive NOS (cNOS), which is activated by Ca 2ϩ and calmodulin, in rat and mouse pancreatic islet cells, i.e., neuronal NOS in ␣-, ␤-, and ␦-cells (3, 25) and endothelial NOS in ␣-and ␦-cells (37). Furthermore, direct biochemical evidence for the cNOS enzyme activity was obtained from isolated islets of mice (33). These findings suggest a physiological involvement of NO in the regulation of the hormone secretion from pancreatic islet cells.By binding to iron in the heme at the active site of soluble guanylate cyclase (sGC), NO activates the enzyme, which results in elevation of the cGMP level. Given that the enzyme activities of guanylate cyclase (16) and cGMP-dependent protein kinase have been demonstrated in pancreatic islets (23), it is plausible that NO ...

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Nitric oxide-cyclic GMP system potentiates glucose-induced rise in cytosolic Ca2+ concentration in rat pancreatic β-cells

Cited by 20 publications

References 33 publications

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

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

Cyclic nucleotide phosphodiesterases in pancreatic islets

Dual effect of nitric oxide on cytosolic Ca²⁺concentration and insulin secretion in rat pancreatic β-cells

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Nitric oxide-cyclic GMP system potentiates glucose-induced rise in cytosolic Ca2+ concentration in rat pancreatic β-cells

Cited by 20 publications

References 33 publications

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

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

Cyclic nucleotide phosphodiesterases in pancreatic islets

Dual effect of nitric oxide on cytosolic Ca2+concentration and insulin secretion in rat pancreatic β-cells

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Dual effect of nitric oxide on cytosolic Ca²⁺concentration and insulin secretion in rat pancreatic β-cells