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Query: UMLS:C0406810 (NAME)
 13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mean plasma insulin concentration was reduced and mean plasma glucose concentration increased following the administration of N-nitro-L-arginine methyl ester (L-NAME; 100 mumol kg-1 i.a.) in conscious calves given continuous infusions of exogenous glucose (30-60 mumol min-1 kg-1 i.v.). It is concluded that the rise in plasma insulin concentration which occurs in these animals in response to glucose is mediated, at least in part, by a nitric oxide-related factor (NOx).
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PMID:Nitric oxide-related pancreatic endocrine responses to hyperglycaemia in the conscious calf. 807 May 33

Although an increased prevalence of hypertension is associated with insulin-dependent diabetes, little is known about the effect of streptozotocin (STZ) diabetes on arterial pressure (AP) regulation in rats. Changes in AP induced by STZ, as well as associated factors in blood pressure regulation such as baroreflex sensitivity, plasma renin activity (PRA), plasma glucose and insulin levels and endothelium participation, were studied in male Wistar rats weighing 287 +/- 10 g. The same seven conscious rats were used for all measurements before and after STZ diabetes. AP pulses were stored on a videotape recorder and processed by a data acquisition system. Baroreflex sensitivity was evaluated by measuring heart rate (HR) changes induced by AP variations produced by phenylephrine and sodium nitroprusside injection. The effect of inhibition of nitric oxide synthesis with NG-nitro-L-arginine methyl ester (L-NAME, 10 mg/kg i.v. bolus plus infusion at 20 mg kg-1 h-1) on AP was evaluated in another set of rats (6 normal and 5 submitted to STZ treatment). STZ induced hyperglycemia (306 +/- 19 mg/dl), a reduction in mean arterial pressure (MAP, from 116 +/- 5 to 101 +/- 4 mmHg) and no changes in HR (320 +/- 10 vs 298 +/- 14 bpm). The tachycardic response to arterial pressure decreases was impaired (-2.29 +/- 0.5 vs -4.5 +/- 0.7 bpm/mmHg, in control) while the bradycardic response to arterial pressure increases was unchanged. Pressure responsiveness to phenylephrine was impaired after STZ (3.78 +/- 0.4 vs 6.73 +/- 0.8 mmHg microU-1 ml-1, in control).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Streptozotocin diabetes modifies arterial pressure and baroreflex sensitivity in rats. 852 May 49

In isolated pancreative beta cells from rats the insulin secretory response to glucose is amplified by L-arginine. Since this effect is inhibited by NO synthesis inhibitors, and since L-arginine is precursor of NO, the observation indicates a role for NO in insulin secretion from beta cells. We recently reported that i.v. L-arginine elicited insulin secretion in anaesthetized rats by a mechanism that was partly NO dependent. The aim of the present study was to assess if the insulin secretory response to an intravenous infusion of glucose also requires an intact NO formation. Anaesthetized rats were given D-glucose (100 mg kg-1 min-1 i.v. for 30 min). Plasma insulin (PI), blood glucose (BG) levels and mean arterial blood pressure (MAP) were assessed from before and until 15 min after the end of the infusion. One group of rats were untreated and served as controls. The two other groups were pretreated with either of the NO synthase inhibitors NW-nitro-L-arginine methyl ester (L-NAME, 50 mg kg-1 i.v.), or NG-monomethyl-L-arginine (L-NMMA, 100 mg kg-1 i.v.). In controls infusion of glucose elevated PI by up to 25 +/- 3 U L-1, and BG by up to 27 +/- 1 mmol L-1. Pretreatment with L-NAME elevated MAP from 74 +/- 6 to 132 +/- 4 mmHg, indicating that NO synthase was inhibited.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The insulin secretory response to intravenous glucose in the rat is independent of NO formation. 855 78

1. We studied a possible interplay of pancreatic NO synthase activity on insulin secretion induced by different beta cell secretagogues and also on pancreatic vascular bed resistance. 2. This study was performed in the isolated perfused pancreas of the rat. Blockage of NO synthase was achieved with Nw-nitro-L-arginine methyl ester (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 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. beta cell responses to KCl (5 mM) and tolbutamide (0.185 mM) were only slight 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 beta 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 microM was ineffective but at 30 microM substantially reduced to 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 response.
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PMID:Alterations of insulin response to different beta cell secretagogues and pancreatic vascular resistance induced by N omega-nitro-L-arginine methyl ester. 864 Mar 33

1. There is evidence that endothelial dysfunction is associated with diabetes mellitus. The purpose of the present study was to assess local cerebral blood flow (LCBF) and cerebrovascular responsiveness to the NOS inhibitor NG-nitro-L-arginine methyl ester (L-NAME) in spontaneously diabetic insulin-dependent BioBred (BB) rats. 2. Diabetic rats, and non-diabetic controls, were treated with L-NAME (30 mg kg-1, i.v.) or saline, 20 min prior to the measurement of LCBF by the fully quantitative [14C]-iodoantipyrine autoradiographic technique. 3. There were no significant differences in physiological parameters (blood pH, PCO2, and PO2, rectal temperature, arterial blood pressure, or plasma glucose) between any of the groups of rats, and no difference in either the extent or the temporal characteristics of the hypertensive response to L-NAME between diabetic and non-diabetic rats. 4. In diabetic rats, a global reduction in basal LCBF was observed, although significant reductions (between -20 and -30%) were found in only 5 (mainly subcortical) out of the 13 brain regions measured. Following L-NAME injection, significant reductions in LCBF (between -20 and -40%) were found in the non-diabetic animals. In diabetic animals treated with L-NAME, a significant reduction in LCBF was measured only in the hypothalamus (-33%). 5. The cerebrovascular response to acute L-NAME is attenuated in spontaneously diabetic insulin-dependent BB rats. This would be consistent with the endothelial dysfunction in cerebral vessels, known to be associated with diabetes mellitus and it is possible that a loss of NO-induced dilator tone, amongst other factors, may underlie the observed reductions of basal LCBF in these animals.
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PMID:Cerebrovascular responsiveness to NG-nitro-L-arginine methyl ester in spontaneously diabetic rats. 873 22

Recent immunohistochemical findings suggested that a constitutive nitric oxide synthase (cNOS) resides in endocrine pancreas. Here we provide direct biochemical evidence for the presence of cNOS activity in isolated islets. The regulating influence of this nitric oxide synthase (NOS) activity for islet hormone release was also investigated. We observed that cNOS activity could be quantitated in islet homogenates by monitoring the formation of L-citrulline from L-arginine using an Amprep CBA cation-exhange minicolumn before derivatization with o-phthaldialdehyde and subsequent high-performance liquid chromatography analysis. The islet NOS was dependent on both Ca2+ and calmodulin and suppressed by the NOS inhibitor NG-nitro-L-arginine methyl ester (L-NAME). This effect was enantiomerically specific. Islet insulin release induced by a mixture of L-arginine and glucose was enhanced by L-NAME, whereas L-arginine-induced glucagon release was inhibited. The effect of L-NAME on insulin release was dose dependently potentiated by increasing glucose concentrations, suggesting that glucose is an important regulator of islet NO production. Complementary in vivo studies showed similar results, i.e., the insulin secretory response to a mixture of glucose and L-arginine was extremely enhanced by pretreatment with L-NAME, whereas L-arginine-stimulated glucagon response was suppressed. Finally, in isolated islets, the intracellular nitric oxide (NO) donor hydroxylamine suppressed insulin release and increased glucagon release. In summary, the islets of Langerhans contain a constitutive, Ca2+/calmodulin-dependent isoform of NOS. Islet NO suppressed insulin but enhanced glucagon secretion. The data also suggest a negative feedback by NO on glucose-induced insulin release. The islet NO system is a novel and important regulatory factor in insulin and glucagon secretion.
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PMID:Islet constitutive nitric oxide synthase: biochemical determination and regulatory function. 876 45

Hypertension is associated with insulin-resistant states such as diabetes and obesity. Nitric oxide (NO) contributes to regulation of blood pressure. To gain insight into potential mechanisms linking hypertension with insulin resistance we directly measured and characterized NO production from human umbilical vein endothelial cells (HUVEC) in response to insulin using an amperometric NO-selective electrode. Insulin stimulation of HUVEC resulted in rapid, dose-dependent production of NO with a maximal response of approximately 100 nM NO (200,000 cells in 2 ml media; ED50 approximately 500 nM insulin). Although HUVEC have many more IGF-1 receptors than insulin receptors (approximately 400,000, and approximately 40,000 per cell respectively), a maximally stimulating dose of IGF-1 generated a smaller response than insulin (40 nM NO; ED50 approximately 100 nM IGF-1). Stimulation of HUVEC with PDGF did not result in measurable NO production. The effects of insulin and IGF-1 were completely blocked by inhibitors of either tyrosine kinase (genestein) or nitric oxide synthase (L-NAME). Wortmannin (an inhibitor of phosphatidylinositol 3-kinase [PI 3-kinase]) inhibited insulin-stimulated production of NO by approximately 50%. Since PI 3-kinase activity is required for insulin-stimulated glucose transport, our data suggest that NO is a novel effector of insulin signaling pathways that are also involved with glucose metabolism.
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PMID:Insulin-stimulated production of nitric oxide is inhibited by wortmannin. Direct measurement in vascular endothelial cells. 877 Aug 59

While essential hypertension may be characterized by insulin resistance, it is unclear which defect is primary. We therefore compared normotensive Sprague-Dawley male rats who drank N-nitro-L-arginine methyl ester (L-NAME, 1 mg/mL in distilled water), with control rats who drank distilled water. Blood pressure was measured noninvasively, weight was controlled by dietary restriction, and glucose tolerance was assessed via oral glucose tolerance tests (OGTT). Blood pressure rose by the second day of L-NAME treatment, and remained elevated throughout the study, in contrast to the rats drinking water (P < .001). Weight rose similarly in both groups. OGTT were performed after 2 weeks of L-NAME. Serum glucose and insulin responses, assessed by two-way ANOVA, were similar in the two groups (P = NS). In summary, L-NAME administration resulted in hypertension, but not a deterioration in glucose tolerance in diet-controlled Sprague-Dawley rats. We conclude that the insulin resistance of some hypertensive states is not the result of hypertension per se, or increased vasoconstriction, such as might result from inhibition of endogenous nitric oxide synthesis, but rather indicates a fundamental metabolic disorder.
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PMID:Oral administration of the nitric oxide biosynthesis inhibitor, N-nitro-L-arginine methyl ester (L-NAME), causes hypertension, but not glucose intolerance or insulin resistance, in rats. 884 69

1. Several recent in vitro studies have suggested that production of nitric oxide (NO) from the islet NO system may have an important regulatory influence on the secretion of insulin and glucagon. In the present paper we have investigated, mainly with an in vivo approach, the influence and specificity of the NO synthase (NOS) blocker NG-nitro-L-arginine methyl ester (L-NAME) on L-arginine-induced secretion of insulin and glucagon. 2. In freely fed mice, L-NAME pretreatment (1.2 mmol kg-1) influenced the dynamics of insulin and glucagon release following an equimolar dose of L-arginine, the specific substrate for NOS activity, in that the NOS inhibitor enhanced the insulin response but suppressed the glucagon responses. This was reflected in a large decrease in the plasma glucose levels of the L-NAME pretreated animals. 3. L-NAME pretreatment did not influence the insulin and glucagon secretory responses to the L-arginine-enantiomer D-arginine, which cannot serve as a substrate for NOS activity. 4. Replacing L-NAME pretreatment by pretreatment with D-arginine or L-arginine itself, which both carry the same cationic change and are devoid of NOS inhibitory properties, did not mimic the effects of L-NAME on L-arginine-induced hormone release. 5. Fasting the animals for 24 h totally abolished the L-NAME-induced potentiation of L-arginine stimulated insulin release suggesting that the sensitivity of the beta-cell secretory machinery to NO-production is greatly changed in the fasting state. However, the L-NAME-induced suppression of L-arginine stimulated glucagon release was unaffected by starvation. 6. In isolated islets from freely fed mice, L-arginine (5 mM) stimulated insulin release was greatly enhanced and glucagon release markedly suppressed by the presence of the NOS inhibitor L-NAME in the incubation medium. These effects were abolished in isolated islets taken from 24 h fasted mice. 7. Our present results, which showed that the NOS inhibitor L-NAME markedly enhances insulin release but suppresses glucagon release induced by L-arginine in the intact animal, give strong support to our previous hypothesis that the islet NO system is a negative modulator of insulin secretion and a positive modulator of glucagon secretion. Additionally, we observed that the importance of the beta-cell NO-production for secretory mechanisms, as evaluated by the effect of L-NAME on L-arginine-induced insulin release, was greatly changed after starvation, an effect less prominent with regard to glucagon release.
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PMID:Interaction of the islet nitric oxide system with L-arginine-induced secretion of insulin and glucagon in mice. 890 52

Previous studies have demonstrated that the nitric oxide (NO) synthase inhibitor L-NAME exerts positive effects on the arginine vasopressin (AVP) and oxytocin (OT) responses to insulin-induced hypoglycemia, suggesting inhibitory actions of NO. The present study was designed to determine whether a gamma-aminobutyric acid (GABA)ergic pathway is involved in regulation of NO action. AVP and OT secretory patterns during insulin (0.15 IU/kg, i.v.)-tolerance tests (ITT) were examined in seven normal male subjects with (experimental tests) and without (control test) concomitant treatment with L-NAME (40 micrograms/kg injected plus 50 micrograms/kg infused, i.v.), the GABAergic agent sodium valproate (600 mg in three divided doses orally) or the combination of L-NAME and sodium valproate. Insulin-induced hypoglycemia increased by 2-fold (peak vs. baseline) plasma AVP and OT levels. In the presence of L-NAME, plasma AVP and OT levels rose 3-fold in response to hypoglycemia and were significantly higher than those in the control test. Administration of sodium valproate alone changed neither AVP nor OT secretory patterns during ITT. In contrast, sodium valproate abolished the facilitating effect of L-NAME on both AVP and OT responses to hypoglycemia. In the ITT plus L-NAME plus sodium valproate test, plasma AVP and OT levels were not significantly different at any time point from those observed during the control ITT. These data indicate a GABAergic mediation of the inhibitory modulation by NO of the AVP and OT responses to insulin-induced hypoglycemia.
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PMID:Gamma-aminobutyric acid mediation of the inhibitory effect of nitric oxide on the arginine vasopressin and oxytocin responses to insulin-induced hypoglycemia. 895 1


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