UMLS:C0406810 - FACTA Search

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

This study was conducted to determine the effect of stevioside (SVS) on glucose metabolism. The experiments were performed in male Wistar rats treated with SVS either by intravenous infusion or feeding. SVS infusion (150 mg/mL) was carried out in doses of 0.67, 1.00, and 1.33 mL.kg-1 body weight.h-1. The plasma glucose level significantly increased both during and after SVS infusion, whereas it was not affected by SVS feeding (13.3 mL.kg-1 body weight). The glucose turnover rate (GTR) of [14C(U)]glucose and [3(-3)H]glucose was not significantly different between control and SVS infusion animals. Percent glucose carbon recycling and glucose clearance were reduced from 28.7 +/- 1.3 to 23.0 +/- 1.6% (p < 0.05) and from 6.46 +/- 0.34 to 4.99 +/- 0.20 mL.min-1.kg-1 body weight (p < 0.01), respectively. The plasma insulin level did not change, whereas the plasma glucose level significantly increased from 120.3 +/- 5.9 to 176.8 +/- 10.8 mg% (p < 0.01) during SVS infusion. Animals pretreated with angiotensin II and arginine vasopressin showed no significant effect, while animals pretreated with prazosin had an attenuated hyperglycemic effect of SVS infusion. Pretreatment with indomethacin or N omega-nitro-L-arginine methyl ester (L-NAME) alleviated the plasma glucose level during the second period of SVS infusion. Pretreatment with the combination infusion of indomethacin and L-NAME reduced the plasma glucose level from 117.0 +/- 1.8 to 109.0 +/- 1.7 mg% (p < 0.001), and normalized the plasma glucose level in the second period of SVS infusion. Insulin infusion inhibited the hyperglycemic effect of SVS infusion. The present results show that the elevation of the plasma glucose level during SVS infusion is not due to the reduction of the insulin level. It is probably the effect of SVS on glucose transport across the cell. Insulin response to a high plasma glucose level is suppressed during SVS infusion. Several interactions among norepinephrine, prostaglandin, and nitric oxide are involved in modulating the hyperglycemia during SVS infusion.
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PMID:The effect of stevioside on glucose metabolism in rat. 936 11

We previously reported the impaired HCO3- secretion and the increased mucosal susceptibility to acid in the duodenum of streptozotocin (STZ)-induced diabetic rats. In this study, we investigated the salutary effect of the NO synthase inhibitor L-NAME (NG-nitro-L-arginine methyl ester) on these changes and compared it with those of insulin. Animals were injected streptozotocin (STZ: 70 mg/kg, ip) and used after 1, 3-4, and 5-6 weeks of diabetes with blood glucose levels of > 300 mg/dL. Under urethane anesthesia the HCO3- secretion was measured in the proximal duodenal loop using a pH-stat method and by adding 10 mM HCl. L-NAME (20 mg/kg x 2) or insulin (4 units/rat) was administered sc for 4-5 weeks, starting 1 week after STZ treatment. The duodenal HCO3- secretory responses to various stimuli such as mucosal acidification (10 mM HCl for 10 min), 16,16-dimethyl prostaglandin E2 (dmPGE2: 10 micrograms/kg, i.v.), and vagal stimulation (0.5 mA, 2 ms, 3 Hz) were significantly decreased in STZ-treated rats, depending on the duration of diabetes. Repeated administration of L-NAME, starting from 1 week after STZ treatment, significantly reduced blood glucose levels toward normal values and restored the HCO3- responses to various stimuli in STZ rats, the effects being similar to those observed after supplementation of insulin. Diabetic rats developed duodenal lesions after perfusion of the duodenum with 150 mM HCl for 4 h, but this ulcerogenic response was significantly inhibited by the repeated treatment with L-NAME as well as insulin. We conclude that L-NAME is effective in ameliorating hyperglycemic conditions in STZ-diabetic rats, similar to insulin, and restores the impaired HCO3- secretion and the increased mucosal susceptibility to acid in diabetic rat duodenums.
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PMID:Impaired duodenal bicarbonate secretion in diabetic rats. Salutary effect of nitric oxide synthase inhibitor. 940 1

Peroxynitrite (1-100 microM) induced a concentration-dependent relaxation of rat aortic rings; the logEC50 and maximum relaxation on endothelium-denuded rings were -5.31 +/- 0.03 and 105 +/- 5%, n = 6, respectively. The presence of the endothelium significantly impaired this relaxation (logEC50, -4.41 +/- 0.04; maximum relaxation, 71 +/- 4%; n = 6); an effect which was reversed by the inhibitor of nitric oxide synthase, N(G)-nitro-L-arginine methyl ester (L-NAME; 100 microM). Incubation with a high concentration of peroxynitrite (1 mM, 10 min followed by washout) had no effect on subsequent relaxation to acetylcholine (0.01-1 microM). It did, however, significantly depress subsequent contraction to phenylephrine (1-300 nM). This depression was dependent upon the presence of D-glucose in the Krebs solution, could be reversed by the inhibitor of soluble guanylate cyclase, methylene blue (10 microM) and reversed spontaneously after 2 h. When peroxynitrite (1 mM) was mixed with D-glucose (11 mM) and subsequently neutralised to remove unreacted peroxynitrite, a new more potent relaxant was formed. Despite this, the ability of peroxynitrite (1-100 microM) to produce relaxation of endothelium-denuded rings was similar in normal and glucose-free Krebs. Glycerol (22 mM), which like D-glucose is membrane permeant, also reacted with peroxynitrite (1 mM) to form a new more potent relaxant. L-cysteine (1 mM) had no effect by itself on the tone of aortic rings and when present in the tissue bath had no effect on the ability of peroxynitrite or neutralised peroxynitrite (1-100 microM) to produce relaxation. It did, however, potentiate the relaxant actions of the products formed from the reaction of peroxynitrite with D-glucose or glycerol. The membrane impermeant sugars, mannitol and sorbitol (each 11 mM) also reacted with peroxynitrite (1 mM), but expression of the vasorelaxant properties of their respective derivatives was seen only in the presence of L-cysteine (1 mM). Membrane permeance cannot, however, explain why peroxynitrite reacts with D-glucose and glycerol, but not mannitol or sorbitol to form products with intrinsic relaxant activity, as the product formed from the impermeant sugar, L-glucose (11 mM), also has intrinsic activity. The relaxant potency of this product was equipotent to that formed from D-glucose and was also potentiated by L-cysteine (1 mM). These result confirm that peroxynitrite can react with glucose and other compounds with alcohol functional groups to form vasorelaxant species. The relaxation induced when peroxynitrite is added to rat aortic rings is not, however, dependent upon this reaction since it occurs in glucose-free Krebs.
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PMID:The effects of peroxynitrite on rat aorta: interaction with glucose and related substances. 940 2

The inhibitory effects of a potent nitric oxide (NO) synthase inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME), on 2-deoxy-D-glucose (2-DG)-induced hyperglycemia were investigated in rats. L-NAME significantly inhibited 2-DG-induced hyperglycemia, although N(G)-nitro-D-arginine methyl ester (D-NAME) did not affect it. A similar NO synthase inhibitor, N(G)-monomethyl-L-arginine (L-NMMA), also inhibited 2-DG-induced hyperglycemia. The antagonistic effects of L-NAME are unrelated to the cholinergic system, since the muscarinic receptor antagonist scopolamine did not affect 2-DG-induced hyperglycemia. The neuronal NO synthase inhibitor 7-nitroindazole (7-NI) did not reduce 2-DG-induced hyperglycemia, but rather enhanced it. Our results suggest that NO may be involved in glucose homeostasis and that the inhibitory effects of L-NAME on 2-DG-induced hyperglycemia are not related to muscarinic receptors or neuronal NO synthase.
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PMID:Inhibitory effects of a nitric oxide synthase inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME), on 2-deoxy-D-glucose-induced hyperglycemia in rats. 944 10

ATP-dependent potassium channel blockers used as hypoglycaemic agents may have effects on vascular disease in diabetes mellitus beyond their effect on blood glucose control. This study was designed to determine the effects of treatment with gliclazide on the isolated abdominal aorta of diabetic rabbits in which endothelium-dependent relaxation is impaired by a mechanism involving oxygen-derived free radicals. After induction of diabetes with alloxan, there was no effect of gliclazide (10 mg x kg(-1) day(-1) orally) on blood glucose or insulin levels over a 6 week period. Hence, this permitted an examination of the vascular effects of gliclazide in diabetic rabbits exclusive of metabolic effects. Acetylcholine- and nitric oxide-induced relaxation in aortae from rabbits treated with or without gliclazide were measured in the absence or presence of the nitric oxide synthase inhibitor, N(G)-nitro-L-arginine (L-NAME). Diabetes was associated with significant impairment of acetylcholine-induced endothelium-dependent relaxation of the abdominal aorta which was not significant in diabetic rabbits treated with gliclazide in vivo. Aortae from diabetic rabbits studied in the presence of L-NAME showed an exaggerated contraction to acetylcholine which was prevented in rabbits treated with gliclazide. Gliclazide treatment did not affect the response to acetylcholine of normal rabbit aorta, and gliclazide when added in vitro had no effect on the response of diabetic rabbit aorta, suggesting that the effect of gliclazide was specific to the abnormality arising with diabetes and was not due to an acute effect of the drug. These data indicate that gliclazide, aside from either a direct antioxidant action or an effect on insulin or glucose levels, may ameliorate diabetic endothelial cell dysfunction.
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PMID:Vascular action of the hypoglycaemic agent gliclazide in diabetic rabbits. 949 23

Vascular endothelial growth factor (VEGF) stimulates nitric oxide (NO) production by endothelial cells in vitro and in vivo. However, the impact of VEGF on inducible nitric oxide synthase (iNOS) activity and NO synthesis in cultured mesangial cells is not known. Therefore, we measured nitrite accumulation in cytokine-stimulated, rat mesangial cells (RMC) in response to graded concentrations of VEGF. Addition of VEGF (10-50 ng/ml) did not alter RMC viability or NO production in either normal (5.6 mM) or high (33.3 mM) glucose conditions. Exposure of RMC to VEGF did not modify the effects of L-arginine (20 mM) or L-NAME (1 mM) on nitrite accumulation in normal or high glucose media. The steady state abundance of iNOS mRNA and the cytosolic content of iNOS protein were unaffected by addition of VEGF. Cultured RMC expressed the high-affinity tyrosine kinase VEGF receptors, flt and flk/KDR, and the levels were not modulated by incubation in normal or high glucose media. We conclude that VEGF does not regulate proliferation or NO production in cultured RMC. These findings suggest that disturbances in the normal interaction between VEGF and NO are not involved in the pathogenesis of abnormal mesangial cell structure or function in diabetic nephropathy.
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PMID:Effect of vascular endothelial growth factor on nitric oxide production by cultured rat mesangial cells. 957 Nov 72

The purpose of this study was to investigate whether in vivo nitric oxide synthase (NOS) inhibition influences insulin-mediated glucose disposal in rat peripheral tissues. The NOS inhibitor NG-nitro-L-arginine methyl ester (L-NAME) or saline was infused constantly during a hyperinsulinemic-euglycemic clamp in normal rats. Glucose utilization rates of insulin-sensitive tissues (individual muscles, heart, and adipose tissues) were simultaneously determined using tracer infusion of 2-deoxy-D-[3H]glucose (2-[3H]DG). NOS blockade with L-NAME resulted in significant (P < 0.05) reduction in both whole body glucose disposal (-16%, P < 0.01) and plasma 2-[3H]DG disappearance rate (-30%, P < 0.05) during hyper-insulinemic-euglycemic clamp. L-NAME significantly decreased insulin-stimulated glucose uptake in heart (-62%, P = 0.01), soleus (-42%, P = 0.05), red (-53%, P < 0.001) and white (-62%, P < 0.001) gastrocnemius, tibialis (-57%, P < 0.01), and quadriceps (-33%, P < 0.05) muscles. The NOS inhibitor also decreased insulin action in brown interscapular (-47%, P < 0.01), retroperitoneal (-52%, P = 0.07), and gonadal (-66%, P = 0.06) adipose tissues. In contrast to in vivo NOS blockade, L-NAME failed to affect basal or insulin-stimulated 2-[3H]DG transport in isolated soleus or extensor digitorum longus muscles in vitro. These results support the hypothesis that the action of insulin to augment glucose uptake by skeletal muscles and other peripheral insulin-sensitive tissues in vivo is NO dependent.
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PMID:Insulin stimulation of glucose uptake in skeletal muscles and adipose tissues in vivo is NO dependent. 957 31

Using infant piglets, we studied the effects of nonspecific inhibition of nitric oxide (NO) synthase by NG-nitro-L-arginine methyl ester (L-NAME; 3 mg/kg) on vascular pressures, regional blood flow, and cerebral metabolism before 8 min of cardiac arrest, during 6 min of cardiopulmonary resuscitation (CPR), and at 10 and 60 min of reperfusion. We tested the hypotheses that nonspecific NO synthase inhibition 1) will attenuate early postreperfusion hyperemia while still allowing for successful resuscitation after cardiac arrest, 2) will allow for normalization of blood flow to the kidneys and intestines after cardiac arrest, and 3) will maintain cerebral metabolism in the face of altered cerebral blood flow after reperfusion. Before cardiac arrest, L-NAME increased vascular pressures and cardiac output and decreased blood flow to brain (by 18%), heart (by 36%), kidney (by 46%), and intestine (by 52%) compared with placebo. During CPR, myocardial flow was maintained in all groups to successfully resuscitate 24 of 28 animals [P value not significant (NS)]. Significantly, L-NAME attenuated postresuscitation hyperemia in cerebellum, diencephalon, anterior cerebral, and anterior-middle watershed cortical brain regions and to the heart. Likewise, cerebral metabolic rates of glucose (CMRGluc) and of lactate production (CMRLac) were not elevated at 10 min of reperfusion. These cerebral blood flow and metabolic effects were reversed by L-arginine. Flows returned to baseline levels by 60 min of reperfusion. Kidney and intestinal flow, however, remained depressed throughout reperfusion in all three groups. Thus nonspecific inhibition of NO synthase did not adversely affect the rate of resuscitation from cardiac arrest while attenuating cerebral and myocardial hyperemia. Even though CMRGluc and CMRLac early after resuscitation were decreased, they were maintained at baseline levels. This may be clinically advantageous in protecting the brain and heart from the damaging effects of hyperemia, such as blood-brain barrier disruption.
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PMID:Hemodynamic effects of nitric oxide synthase inhibition before and after cardiac arrest in infant piglets. 957 43

NG-nitro-L-arginine methyl ester (L-NAME; 250 micrograms/5 microliters), an inhibitor of NO synthase, or the vehicle artificial cerebrospinal fluid (aCSF; 5 microliters) was administered intracerebroventricularly to conscious rats hemorrhaged (0.7 ml/min) to a 20% volume depletion. Hypotension was maximal 5 min after hemorrhage ended, with compensatory recovery to basal levels 20 min later, regardless of drug treatment. L-NAME, however, elevated (P < 0.05) blood pressure (vs. aCSF controls) 40-45 min after intracerebroventricular administration. In normovolemic rats, L-NAME produced a significant pressor response and increased plasma levels of vasopressin (VP) and oxytocin (OT). After hemorrhage, both hormone levels increased, but only OT was further enhanced by L-NAME. Thus centrally produced NO tonically inhibits OT and VP secretion under basal normovolemic conditions and selectively inhibits OT release during hypovolemia. Hemorrhage increased the rates of glucose utilization in the neural lobe, indicative of enhanced efferent neural functional activity. L-NAME further enhanced the metabolic activity in the entire hypothalamoneurohypophysial system of hemorrhaged animals. Several other brain structures involved in the regulation of blood pressure and the stress response were also metabolically affected by the hemorrhage and L-NAME.
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PMID:Effects of L-NAME on cerebral metabolic, vasopressin, oxytocin, and blood pressure responses in hemorrhaged rats. 957 71

The role of mitochondrial energy metabolism in glutamate mediated neurotoxicity was studied in rat neurones in primary culture. A brief (15 min) exposure of the neurones to glutamate caused a dose-dependent (0.01-1 mM) increase in cyclic GMP levels together with delayed (24 h) neurotoxicity and ATP depletion. These effects were prevented by either the nitric oxide (.NO) synthase (NOS) inhibitor Nomega-nitro-L-arginine methyl ester (NAME; 1 mM) or by the N-methyl-D-aspartate (NMDA) glutamate-subtype receptor antagonist D-(-)-2-amino-5-phosphonopentanoate (APV; 0.1 mM). Glutamate exposure (0.1 mM and 1 mM) followed by 24 h of incubation caused the inhibition of succinate-cytochrome c reductase (20-25%) and cytochrome c oxidase (31%) activities in the surviving neurones, without affecting NADH-coenzyme-Q1 reductase activity. The rate of oxygen consumption was impaired in neurones exposed to 1 mM glutamate, either with glucose (by 26%) or succinate (by 39%) as substrates. These effects on the mitochondrial respiratory chain and neuronal respiration, together with the observed glutathione depletion (20%) by glutamate exposure were completely prevented by NAME or APV. Our results suggest that mitochondrial dysfunction and impairment of antioxidant status may account for glutamate-mediated neurotoxicity via a mechanism involving .NO biosynthesis.
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PMID:Glutamate neurotoxicity is associated with nitric oxide-mediated mitochondrial dysfunction and glutathione depletion. 959 99

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