Insulin Secretion from Pancreatic B Cells Caused by L-Arginine-Derived Nitrogen Oxides

Schmidt, Harald; Warner, Timothy D.; Ishii, Kunio; Sheng, Hong; Murad, FeridF

doi:10.1126/science.1371193

Cited by 396 publications

(238 citation statements)

References 29 publications

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“…the fi cell physiological stimulus, with respect to the conflicting reports as to the ability of glucose to induce NO formation (Jones et al, 1992;Schmidt et al, 1992) our data agree with an activation of the constitutive form of NO synthase by glucose. However, unlike the stimulating effect on insulin secretion previously proposed, our results bring evidence for an inhibitory effect; addition of L-NAME at increasing concentrations, when performed prior to and during high glucose, progressively converted the biphasic pattern of fi cell response into a greater monophasic one, whereas D-NAME was without effect.…”

Section: Discussionsupporting

confidence: 81%

Alterations of insulin response to different β cell secretagogues and pancreatic vascular resistance induced by N^ω‐nitro‐L‐arginine methyl ester

Gross

Roye

Manteghetti

et al. 1995

British J Pharmacology

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1 We studied a possible interplay of pancreatic NO synthase activity on insulin secretion induced by different P cell secretagogues and also onf pancreatic vascular bed resistance. 2 This study was performed in the isolated perfused pancreas of the rat. Blockade of NO synthase was achieved with N"-nitro-L-arginine methyl estr (L-NAME); the specificity of the antagonist was checked by using its D-enantiomer as well as by substitutive treatments with sodium nitroprusside (SNP) as a NO donor in studies of glucose-induced insulin secretion. 3 Arginine (5 mM) induced a monophasic -insulin response which was, in the presence of L-NAME at equimolar concentration, very strongly potentiated and converted into a 13 times higher biphasic one. D-NAME (5 mM) was only able to induce a 3 times higher response, but provoked a similar vasoconstrictor effect. 4 The small biphasic insulin secretion induced by L-leucine (5 mM) was also strongly enhanced, by 8 times, in the presence of L-NAME (5 mm) vs 2 times in the presence of D-NAME (5 mM). 5 f cell responses to KCl (5 mM) and tolbutamide (0.185 mM) were only slightly increased by L-NAME (5 mM) to values not far from the sum of the effects of L-NAME and of the two drugs alone. D-NAME (5 mM) was totally ineffective on the actions of both secretagogues. 6 L-NAME, infused 15 min before and during a rise in glucose concentration from 5 to 11 mm, was able in the low millimolar range (0.1-0.5 mM) to blunt the classical biphasic pattern of fi cell response to glucose and, at 5 mm, to convert it into a significantly greater monophasic one. In contrast, D-NAME (5 mM) was unable to induce similar effects. 7 SNP alone at 3 JAM was ineffective but at 30 JM substantially reduced the second phase of insulin response to glucose; however, at both concentrations the NO donor partly reversed alterations in insulin secretion caused by L-NAME (5 mM) and restored a biphasic pattern of insulin response. At a high (300 juM) concentration, SNP drastically reduced the second phase of f cell response, but in the presence of L-NAME, provoked a significantly greater biphasic response.8 When L-NAME was infused only for the 15 min before high glucose, an exaggerated first phase of P cell response was followed by an abortive second one. SNP, at a low concentration (30 nM), given simultaneously with L-NAME, restored a biphasic pattern and prevented the vasoconstrictor effect induced by the inhibitor. 9 L-NAME, when infused only during high glucose, markedly enhanced the second phase of insulin response which could be significantly reduced by SNP (3 aM). The NO donor induced a dilator effect significantly greater in L-NAME-treated pancreata than in non-treated ones. 10 In conclusion our data bring evidence that NO synthase activity exerts an inhibitory control on pancreatic f cell response to various nutrient secretagogues and may, at least partly, be implicated in the generation of the biphasic pattern of insulin response to glucose.

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Section: Discussionsupporting

confidence: 81%

Alterations of insulin response to different β cell secretagogues and pancreatic vascular resistance induced by N^ω‐nitro‐L‐arginine methyl ester

Gross

Roye

Manteghetti

et al. 1995

British J Pharmacology

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“…Similar results have also been reported with regard to isolated rat islets (Cunningham et al 1994, Sjöholm 1996 and the isolated perfused rat pancreas (Gross et al 1995), although some earlier data, mostly obtained from -cell lines, suggested that islet NO production either enhanced or had no effect on nutrient-stimulated insulin secretion (Laychock et al 1991, Jones et al 1992, Schmidt et al 1992.…”

Section: Introductionsupporting

confidence: 75%

“…We and others have previously presented histochemical, immunocytochemical and biochemical evidence, for the occurrence of a constitutive Ca 2+ /calmodulin-dependent nitric oxide synthase (cNOS) activity in mouse and rat islet endocrine cells (Panagiotidis et al 1992, 1994, Schmidt et al 1992, Corbett et al 1993, Henningsson & Lundquist 1998, Åkesson et al 1999, Alm et al 1999, Henningsson et al 1999. Further, in a series of combined in vitro and in vivo experiments in the mouse we observed that selective inhibition of islet NOS activity markedly enhanced insulin release stimulated by glucose or arginine (Panagiotidis et al 1992, 1994, Åkesson et al 1996, 1999, 1998c,d, Henningsson & Lundquist 1998, Henningsson et al 1999.…”

Section: Introductionmentioning

confidence: 99%

Nitric oxide, islet acid glucan-1,4-alpha-glucosidase activity and nutrient-stimulated insulin secretion

Mosén¹,

Salehi²,

Lundquist³

2000

Journal of Endocrinology

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The mechanism of nutrient-evoked insulin release is clearly complex. One part of that mechanism is postulated to be the activation of the glycogenolytic enzyme acid glucan-1,4--glucosidase. As nitric oxide (NO) has been found to be a potent inhibitor of glucose-stimulated insulin secretion, we have now investigated a possible influence of exogenous NO and inhibition of endogenous NO production on islet acid glucan-1,4--glucosidase activity in relation to insulin release stimulated by glucose and -arginine. In isolated islets, NO derived from the intracellular NO donor hydroxylamine inhibited the activation of acid glucan-1,4--glucosidase and its isoform acid -glucosidase in parallel with inhibition of glucosestimulated insulin release. In comparison, other lysosomal enzymes were largely unaffected. Similarly, the spontaneous NO donor sodium nitroprusside, as well as NO gas, when added to islet homogenates, suppressed the activities of these acid -glucosidehydrolases and, to a lesser extent, the activities of other lysosomal enzymes. Finally, in the presence of the NO synthase inhibitor N G -nitro--arginine methyl ester, insulin release from isolated islets stimulated by glucose or -arginine was markedly potentiated in parallel with an accompanying increase in the activities of acid glucan-1,4--glucosidase and acid -glucosidase. Other lysosomal enzymes and neutral -glucosidase were not influenced. We propose that an important inhibitory effect of NO on the insulin secretory processes stimulated by glucose and -arginine is exerted via inactivation of islet acid glucan-1,4--glucosidase, a putative key enzyme in nutrient-stimulated insulin release.

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“…Nitric oxide has been associated with the regulation of pancreatic blood flow and insulin release. The synthesising enzyme nNOS has been found in β-cells of rats (Schmidt et al 1992) and chickens (Ekblad et al 1994 ;Liu et al 1994) and NO may therefore play a regulatory role in islet hormone secretion (Jansson & Sandler, 1991 ;Ekblad et al 1994).…”

Section: mentioning

confidence: 99%

Peptidergic hormones and neuropeptides, and aminergic neurotransmitters of the pancreatic islets of the Houbara bustard (Chlamydotis undulata)

et al. 2000

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Immunoreactivity to insulin (Ins), somatostatin (Som), glucagon (Glu) and pancreatic polypeptide (PP) was found in 70 %, 22 %, 15 % and 11 % respectively of Houbara pancreatic endocrine islet cells. Whilst Ins occurred centrally and SOM was observed both in peripherally and centrally located islets, the other hormones were localised in peripheral islet cells ; Som was also observed in neuronal cell bodies and nerve fibres. In addition, the islet cells contained substance P (SP) (65 %) in the centre and vasoactive intestinal polypeptide (VIP) (2 %) at the periphery. Immunoreactivity to choline acetyltransferase (ChAT), VIP and galanin (Gal) occurred in the walls of blood vessels located mainly at the periphery of islets. Occasionally, VIP and Gal immunoreactive varicose nerve terminals and ChAT immunoreactive cell bodies were also observed in the centre of islets. SP neuronal cell bodies were not observed but prominent SP immunoreactive varicose terminals were discernible in capillary walls within the islets. Neuropeptide Y (NPY) immunoreactive neurons were detected in neuronal cell bodies located mainly peripherally. Neuronal nitric oxide synthase (nNOS) immunoreactivity occurred in neuronal cell bodies and nerve fibres mainly at the periphery and also in centrally located islet endocrine cells. Immunoreactivity to tyrosine hydroxylase (TH) was similar in distribution to that of ChAT. In comparison with other avian species, the islets of the dorsal pancreatic lobe of the bustard contain all the peptidergic hormones normally present in the islets of other avian species, but are not segregated into dark A and light B cells. Many of the insulin containing cells also contained SP. The islets also contained several neuropeptides which are probably involved in their regulation.

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Insulin Secretion from Pancreatic B Cells Caused by L-Arginine-Derived Nitrogen Oxides

Cited by 396 publications

References 29 publications

Alterations of insulin response to different β cell secretagogues and pancreatic vascular resistance induced by N^ω‐nitro‐L‐arginine methyl ester

Alterations of insulin response to different β cell secretagogues and pancreatic vascular resistance induced by N^ω‐nitro‐L‐arginine methyl ester

Nitric oxide, islet acid glucan-1,4-alpha-glucosidase activity and nutrient-stimulated insulin secretion

Peptidergic hormones and neuropeptides, and aminergic neurotransmitters of the pancreatic islets of the Houbara bustard (Chlamydotis undulata)

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Insulin Secretion from Pancreatic B Cells Caused by L-Arginine-Derived Nitrogen Oxides

Cited by 396 publications

References 29 publications

Alterations of insulin response to different β cell secretagogues and pancreatic vascular resistance induced by Nω‐nitro‐L‐arginine methyl ester

Alterations of insulin response to different β cell secretagogues and pancreatic vascular resistance induced by Nω‐nitro‐L‐arginine methyl ester

Nitric oxide, islet acid glucan-1,4-alpha-glucosidase activity and nutrient-stimulated insulin secretion

Peptidergic hormones and neuropeptides, and aminergic neurotransmitters of the pancreatic islets of the Houbara bustard (Chlamydotis undulata)

Contact Info

Product

Resources

About

Alterations of insulin response to different β cell secretagogues and pancreatic vascular resistance induced by N^ω‐nitro‐L‐arginine methyl ester

Alterations of insulin response to different β cell secretagogues and pancreatic vascular resistance induced by N^ω‐nitro‐L‐arginine methyl ester