scholarly journals Nitric oxide stimulates glucose transport and metabolism in rat skeletal muscle in vitro

1997 ◽  
Vol 322 (1) ◽  
pp. 223-228 ◽  
Author(s):  
Martin E. YOUNG ◽  
George K. RADDA ◽  
Brendan LEIGHTON
Keyword(s):  
Nitric Oxide ◽  
Glucose Metabolism ◽  
Glucose Transport ◽  
Glucose Oxidation ◽  
Glycogen Synthesis ◽  
No Donor ◽  
Lactate Release ◽  
Ly 83583 ◽  
Spermine Nonoate

1. The effects of the nitric oxide (NO) donor sodium nitroprusside (SNP) on the rates of glucose transport and utilization and its interaction with insulin were investigated in rat soleus muscle in vitro. SNP stimulated the rate of 2-deoxyglucose transport and insulin-mediated (100 Ɓ-units/ml) rates of both net and [14C]lactate release and the rate of glucose oxidation. The effects of SNP were independent of the concentration-dependent effects of insulin on glucose metabolism. 2. SNP stimulated the insulin-stimulated rates of net and [14C]lactate release and glucose oxidation in a concentration-dependent manner. The rate of [14C]lactate release was also stimulated by another NO donor, (Z)-1-(N-[aminopropyl]-N-[4-(3-aminopropylammonio)butyl]-amino)-diazen-1-ium-1,2-diolate (spermine NONOate). 3. SNP at 5, 10 and 15 mM inhibited the insulin-stimulated rate of glycogen synthesis and this rate was further decreased at 20 and 25 mM SNP. SNP did not affect the rate of glycogen synthesis in the absence of insulin. 4. Haemoglobin, which is a NO scavenger, prevented the stimulation of the rates of [14C]lactate release by SNP or spermine NONOate. 5. The cGMP content was increased maximally (by approx. 80-fold) within 15 min by SNP (15 mM). The cGMP content, raised maximally by SNP, was significantly decreased by the guanylate cyclase inhibitor LY-83583 (10 ƁM). The cGMP analogue 8-bromo-cGMP (100 ƁM) significantly increased the rate of net lactate release. 6. LY-83583 significantly inhibited SNP-stimulated rates of 2-deoxyglucose transport, [14C]lactate release and glucose oxidation. Methylene Blue (another guanylate cyclase inhibitor) also inhibited SNP-stimulated rates of [14C]lactate release. 7. The results suggest that in rat skeletal muscle: (a) nitric oxide (from SNP or spermine NONOate) increases the rate of glucose transport and metabolism, an effect independent of insulin; (b) SNP inhibits insulin-mediated rates of glycogen synthesis; (c) SNP stimulates cGMP formation, which mediates, at least partly, the effects on glucose metabolism; (d) nitric oxide-mediated stimulation of glucose utilization might occur in fibre contraction. The implications of the effects of NO on glucose metabolism are discussed.

Glucose metabolism in rat hypothalamus

1981 ◽  
Vol 98 (4) ◽  
pp. 481-487 ◽  
Author(s):  
Pentti Lautala ◽  
Julio M. Martin
Keyword(s):  
Glucose Metabolism ◽  
Glucose Transport ◽  
Glucose Concentration ◽  
Glucose Oxidation ◽  
Glucose Utilization ◽  
Rat Hypothalamus ◽  
Extracellular Glucose Concentration ◽  
Extracellular Glucose ◽  
Phenazine Methosulphate

Abstract. In vitro glucose oxidation and glucose transport in the rat medial (MH) and lateral (LH) hypothalamic areas was measured. Glucose oxidation was calculated from the conversion of [U-14C]glucose to 14C02 and glucose transport from 14C02 produced from [114C]glucose in the presence of phenazine methosulphate and NaF. Increasing glucose in the medium from 1 him to 20 mm enhanced glucose oxidation two-fold in MH and 40% in LH. Addition of insulin, 100 (iU/ml, to the medium decreased glucose oxidation 30% both in MH and LH at both 4 mm and 20 mm glucose. Fasting did not affect glucose oxidation in either of these hypothalamic areas. Glucose transport was not affected by insulin, but was increased significantly when glucose was raised from 0.25 mm to 1.0 mm. Fasting also increased glucose transport in both hypothalamic areas. In conclusion, extracellular glucose concentration seems to be the major regulator of glucose utilization by the rat hypothalamus. Insulin, rather than increasing, seems to decrease glucose oxidation while having no effect on glucose transport.

Differential effects of lipoic acid stereoisomers on glucose metabolism in insulin-resistant skeletal muscle

1997 ◽  
Vol 273 (1) ◽  
pp. E185-E191 ◽  
Author(s):  
R. S. Streeper ◽  
E. J. Henriksen ◽  
S. Jacob ◽  
J. Y. Hokama ◽  
D. L. Fogt ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Glucose Metabolism ◽  
Glucose Transport ◽  
Lipoic Acid ◽  
Glucose Oxidation ◽  
Glucose Transporter ◽  
Glycogen Synthesis ◽  
Racemic Mixture ◽  
Insulin Resistant ◽  
The Individual

The racemic mixture of the antioxidant alpha-lipoic acid (ALA) enhances insulin-stimulated glucose metabolism in insulin-resistant humans and animals. We determined the individual effects of the pure R-(+) and S-(-) enantiomers of ALA on glucose metabolism in skeletal muscle of an animal model of insulin resistance, hyperinsulinemia, and dyslipidemia: the obese Zucker (fa/fa) rat. Obese rats were treated intraperitoneally acutely (100 mg/kg body wt for 1 h) or chronically [10 days with 30 mg/kg of R-(+)-ALA or 50 mg/kg of S-(-)-ALA]. Glucose transport [2-deoxyglucose (2-DG) uptake], glycogen synthesis, and glucose oxidation were determined in the epitrochlearis muscles in the absence or presence of insulin (13.3 nM). Acutely, R-(+)-ALA increased insulin-mediated 2-DG-uptake by 64% (P < 0.05), whereas S-(-)-ALA had no significant effect. Although chronic R-(+)-ALA treatment significantly reduced plasma insulin (17%) and free fatty acids (FFA; 35%) relative to vehicle-treated obese animals, S-(-)-ALA treatment further increased insulin (15%) and had no effect on FFA. Insulin-stimulated 2-DG uptake was increased by 65% by chronic R-(+)-ALA treatment, whereas S-(-)-ALA administration resulted in only a 29% improvement. Chronic R-(+)-ALA treatment elicited a 26% increase in insulin-stimulated glycogen synthesis and a 33% enhancement of insulin-stimulated glucose oxidation. No significant increase in these parameters was observed after S-(-)-ALA treatment. Glucose transporter (GLUT-4) protein was unchanged after chronic R-(+)-ALA treatment but was reduced to 81 +/- 6% of obese control with S-(-)-ALA treatment. Therefore, chronic parenteral treatment with the antioxidant ALA enhances insulin-stimulated glucose transport and non-oxidative and oxidative glucose metabolism in insulin-resistant rat skeletal muscle, with the R-(+) enantiomer being much more effective than the S-(-) enantiomer.

Effects of Insulin on Glucose Metabolism in Skeletal Muscle from Septic and Endotoxaemic Rats

1989 ◽  
Vol 77 (1) ◽  
pp. 61-67 ◽  
Author(s):  
Brendan Leighton ◽  
George D. Dimitriadis ◽  
Mark Parry-Billings ◽  
Jane Bond ◽  
Paulo R. L. de Vasconcelos ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Glucose Metabolism ◽  
Glucose Transport ◽  
Soleus Muscle ◽  
Glycogen Synthesis ◽  
Dependent Manner ◽  
H 26 ◽  
Lactate Formation ◽  
Dose Dependent

1. The effects of non-lethal bacteraemia or endotoxaemia on insulin-stimulated glucose metabolism were studied in isolated, incubated soleus muscle of rats after 24 and 48 h. 2. The insulin-stimulated rates of lactate formation and glycogen synthesis were similar in muscles isolated from control and bacteraemic rats. 3. Endotoxaemia increased the rates of lactate formation, at all levels of insulin, both at 24 h (∼ 32%) and 48 h (∼ 26%). Endotoxaemia did not alter the sensitivity of glycolysis to insulin. 4. Endotoxaemia decreased the rates of glycogen synthesis at all concentrations of insulin both at 24 h (∼ 39%) and 48 h (∼ 23%). 5. The increase in the rate of glycolysis was related in a dose-dependent manner to the amount of endotoxin given to the animals. 6. Endotoxaemia decreased plasma tri-iodothyronine levels (41%). However, the effects of endotoxaemia (48 h) on glucose metabolism in muscle are similar to those caused by hyperthyroidism. In hypothyroid rats, endotoxin administration increased the rates of glycolysis in muscle in vitro. 7. It is concluded that there are enhanced basal and insulin-stimulated rates of glycolysis in soleus muscle from endotoxaemic rats. This may be due to both increased glucose transport and decreased glycogen synthesis.

Nitric oxide enhances hydrogen peroxide-mediated endothelial permeability in vitro

1997 ◽  
Vol 273 (5) ◽  
pp. C1581-C1587 ◽  
Author(s):  
Naotsuka Okayama ◽  
Christopher G. Kevil ◽  
Loisann Correia ◽  
David Jourd’Heuil ◽  
Makoto Itoh ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Endothelial Permeability ◽  
Reactive Oxygen ◽  
Iron Chelator ◽  
Reactive Oxygen Metabolites ◽  
No Donor ◽  
Spermine Nonoate ◽  
Oxygen Metabolites

The objective of this study was to evaluate the effects of nitric oxide (NO) on H2O2-mediated endothelial permeability. H2O2(0.1 mM) increased permeability at 90 min to 298% of baseline. Spermine NONOate (SNO), an NO donor, at 0.1 or 1 mM did not alter permeability. However, 0.1 mM H2O2+ 1 mM SNO increased permeability to 764%, twice that of 0.1 mM H2O2alone. These treatments were not directly toxic to endothelial cells. This NO effect was concentration dependent, inasmuch as 0.1 mM SNO did not significantly change H2O2-mediated permeability. The NO-enhanced, H2O2-dependent permeability required the simultaneous presence of NO and H2O2, inasmuch as preincubation with SNO for 30 min followed by 0.1 mM H2O2did not alter permeability. Staining of endothelial junctions showed widening of the intercellular space only in junctions of cells exposed to H2O2(0.1 mM) + SNO (1 mM). Furthermore, NO did not affect H2O2metabolism by endothelial cells but significantly depleted intracellular glutathione. This reduction of cell glutathione produced by NO exposure recovered 15–30 min after removal of the NO donor. NO-enhanced permeability was completely blocked by methionine (1 mM), a scavenger of reactive oxygen species, and by the iron chelator desferrioxamine (0.1 mM). These results suggest that NO may exacerbate the effects of H2O2-dependent increase in endothelial monolayer permeability via the iron-catalyzed formation of reactive oxygen metabolites.

Involvement of nitric oxide in inhibitory innervation of urinary bladder of Atlantic cod, Gadus morhua

1996 ◽  
Vol 270 (6) ◽  
pp. R1380-R1385
Author(s):  
C. Olsson ◽  
S. Holmgren
Keyword(s):  
Nitric Oxide ◽  
Urinary Bladder ◽  
Gadus Morhua ◽  
Atlantic Cod ◽  
Maximal Effect ◽  
No Donor ◽  
Beta Adrenoceptor ◽  
Adrenoceptor Antagonist ◽  
Ly 83583

The aim of this study was to investigate the involvement of nitric oxide (NO) in the nonadrenergic, noncholinergic (NANC) relaxation of the urinary bladder of the Atlantic cod, Gadus morhua. NADPH diaphorase-reactive nerve cells, presumed to be able to produce NO, were found in the vesicular nerve. The cells occurred alone and in ganglia together with stained and unstained cells. The effect of inhibitors of NO synthesis on the relaxation was examined in vitro in isolated muscle preparations. NG-nitro-L-arginine methyl ester (10(-4) M) and NG-nitro-L-arginine (L-NNA; 10(-4) M) decreased the electrically induced relaxation to 32 +/- 6 (n = 8) and 28 +/- 6% (n = 8) of the control, respectively. L-Arginine (10(-3) M) increased the relaxation to 152 +/- 24% (n = 8), without affecting the inhibition by L-NNA. The beta-adrenoceptor antagonist propranolol together with L-arginine analogues abolished the relaxation in 7 of 11 preparations. The NO donor sodium nitroprusside (NaNP) caused a concentration-dependent relaxation of the bladder, with a maximal effect obtained at 10(-4) M. LY-83583 (10(-5) M), a guanylate cyclase inhibitor, decreased both the electrically (n = 8) and the NaNP (10(-6) M, n = 9)-induced relaxation to 69 +/- 5 and 20 +/- 4% of the control, respectively. Together these findings suggest that NO is involved in the NANC regulation of the motility of the urinary bladder of the Atlantic cod.

scholarly journals Nitric oxide inhibits glycogen synthesis in isolated rat hepatocytes

1998 ◽  
Vol 330 (2) ◽  
pp. 1045-1049 ◽  
Author(s):  
Fleur SPRANGERS ◽  
P. Hans SAUERWEIN ◽  
A. Johannes ROMIJN ◽  
M. George van WOERKOM ◽  
J. Alfred MEIJER
Keyword(s):  
Nitric Oxide ◽  
Glucose Metabolism ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Glycogen Synthase ◽  
Glycogen Synthesis ◽  
Rat Hepatocytes ◽  
Inhibitory Effect ◽  
No Donor ◽  
Isolated Rat Hepatocytes ◽  
Intracellular Glucose

There is increasing evidence for the existence of intrahepatic regulation of glucose metabolism by Kupffer cell products. Nitric oxide (NO) is known to inhibit gluconeogenic flux through pyruvate carboxylase and phosphoenolpyruvate carboxykinase. However, NO may also influence glucose metabolism at other levels. Using hepatocytes from fasted rats incubated with the NO-donor S-nitroso-N-acetylpenicillamine, we have now found that the synthesis of glycogen from glucose is even more sensitive to inhibition by NO than gluconeogenesis. Inhibition of glycogen production by NO was accompanied by a rise in intracellular glucose 6-phosphate and UDPglucose. Activity of glycogen synthase, as measured in extracts of hepatocytes after the cells had been exposed to NO, was decreased. Experiments with gel-filtered liver extracts revealed that inhibition of glycogen synthase was caused by an inhibitory effect of NO on the conversion of glycogen synthase b into glycogen synthase a.

Effects of modulation of nitric oxide on rat diaphragm isotonic contractility during hypoxia

2003 ◽  
Vol 94 (2) ◽  
pp. 612-620 ◽  
Author(s):  
Xiaoping Zhu ◽  
Leo M. A. Heunks ◽  
Herwin A. Machiels ◽  
Leo Ennen ◽  
P. N. Richard Dekhuijzen
Keyword(s):  
Nitric Oxide ◽  
Power Generation ◽  
Muscle Contraction ◽  
Fatigue Properties ◽  
Rat Diaphragm ◽  
Shortening Velocity ◽  
No Donor ◽  
Diaphragm In Vitro ◽  
Spermine Nonoate

Nitric oxide (NO) is essential for optimal myofilament function of the rat diaphragm in vitro during active shortening. Little is known about the role of NO in muscle contraction under hypoxic conditions. Hypoxia might increase the NO synthase (NOS) activity within the rat diaphragm. We hypothesized that NO plays a protective role in isotonic contractile and fatigue properties during hypoxia in vitro. The effects of the NOS inhibitor N G-monomethyl-l-arginine (l-NMMA), the NO scavenger hemoglobin, and the NO donor spermine NONOate on shortening velocity, power generation, and isotonic fatigability during hypoxia were evaluated (Po 2 ∼ 7 kPa). l-NMMA and hemoglobin slowed the shortening velocity, depressed power generation, and increased isotonic fatigability during hypoxia. The effects ofl-NMMA were prevented by coadministration with the NOS substrate l-arginine. Spermine NONOate did not alter isotonic contractile and fatigue properties during hypoxia. These results indicate that endogenous NO is needed for optimal muscle contraction of the rat diaphragm in vitro during hypoxia.

scholarly journals Effects of hypothyroidism on the sensitivity of glycolysis and glycogen synthesis to insulin in the soleus muscle of the rat

1989 ◽  
Vol 257 (2) ◽  
pp. 369-373 ◽  
Author(s):  
G D Dimitriadis ◽  
B Leighton ◽  
M Parry-Billings ◽  
D West ◽  
E A Newsholme
Keyword(s):  
Fatty Acids ◽  
Glucose Metabolism ◽  
Free Fatty Acids ◽  
Glucose Transport ◽  
Soleus Muscle ◽  
Plasma Levels ◽  
Glucose Oxidation ◽  
Glycogen Synthesis ◽  
Fasting Plasma ◽  
Glucose Phosphorylation

1. The effects of hypothyroidism on the sensitivity of glycolysis and glycogen synthesis to insulin were investigated in the isolated, incubated soleus muscle of the rat. 2. Hypothyroidism, which was induced by administration of propylthiouracil to the rats, decreased fasting plasma levels of free fatty acids and increased plasma levels of glucose but did not significantly change plasma levels of insulin. 3. The sensitivity of the rates of glycogen synthesis to insulin was increased at physiological, but decreased at supraphysiological, concentrations of insulin. 4. The rates of glycolysis in the hypothyroid muscles were decreased at all insulin concentrations studied and the EC50 for insulin was increased more than 8-fold; the latter indicates decreased sensitivity of this process to insulin. However, at physiological concentrations of insulin, the rates of glucose phosphorylation in the soleus muscles of hypothyroid rats were not different from controls. This suggests that hypothyroidism affects glucose metabolism in muscle not by affecting glucose transport but by decreasing the rate of glucose 6-phosphate conversion to lactate and increasing the rate of conversion of glucose 6-phosphate to glycogen. 5. The rates of glucose oxidation were decreased in the hypothyroid muscles at all insulin concentrations.

Endogenous nitric oxide inhibits chloride transport in the thick ascending limb

1999 ◽  
Vol 276 (1) ◽  
pp. F159-F163 ◽  
Author(s):  
Craig F. Plato ◽  
Barbara A. Stoos ◽  
Ding Wang ◽  
Jeffrey L. Garvin
Keyword(s):  
Nitric Oxide ◽  
Chloride Transport ◽  
Thick Ascending Limb ◽  
Chloride Flux ◽  
Nacl Transport ◽  
No Donor ◽  
Endogenous Nitric Oxide ◽  
Spermine Nonoate

Nitric oxide (NO) inhibits transport in various nephron segments, and the thick ascending limb of the loop of Henle (TALH) expresses NO synthase (NOS). However, the effects of NO on TALH transport have not been extensively studied. We hypothesized that endogenously produced NO directly decreases NaCl transport by the TALH. We first determined the effect of exogenously added NO on net chloride flux ( J Cl). The NO donor spermine NONOate (SPM; 10 μM) decreased J Cl from 101.2 ± 9.6 to 65.0 ± 7.7 pmol ⋅ mm−1 ⋅ min−1, a reduction of 35.5 ± 6.4%, whereas controls did not decrease over time. To determine whether endogenous NO affects cortical TALH transport, we measured the effect of adding the NOS inhibitor N G-nitro-l-arginine methyl ester (l-NAME), the substratel-arginine (l-Arg), or its enantiomerd-arginine (d-Arg) on J Cl.l-NAME andd-Arg did not alter J Cl; in contrast, addition of 0.5 mM l-Arg decreased J Cl by 40.2 ± 10.4% from control. The inhibition of chloride flux by 0.5 mM l-Arg was abolished by pretreatment with l-NAME, indicating that cortical TALH NOS is active, but production of NO is substrate-limited in our preparation. Furthermore, cortical TALH chloride flux increased following removal of 0.5 mMl-Arg from the bath, indicating that the reductions in chloride flux observed in response tol-Arg are not the result of NO-mediated cytotoxicity. We conclude that 1) exogenous NO decreases cortical TALH J Cl; 2) cortical TALHs produce NO in the presence of l-Arg, which decreases J Cl; and 3) the response of cortical TALHs to l-Arg is reversible in vitro. These data suggest an important role for locally produced NO, which may act via an autocrine mechanism to directly affect TALH sodium chloride transport. Thus TALH NO synthesis and inhibition of chloride transport may contribute to the diuretic and natriuretic effects of NO observed in vivo.

Nitric oxide preconditioning regulates endothelial monolayer integrity via the heat shock protein 90-soluble guanylate cyclase pathway

2007 ◽  
Vol 292 (2) ◽  
pp. H893-H903 ◽  
Author(s):  
Galina N. Antonova ◽  
Connie M. Snead ◽  
Alexander S. Antonov ◽  
Christiana Dimitropoulou ◽  
Richard C. Venema ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Cell Injury ◽  
Soluble Guanylate Cyclase ◽  
Heat Shock Protein 90 ◽  
Protective Effects ◽  
No Donor ◽  
Spermine Nonoate

Large (pathological) amounts of nitric oxide (NO) induce cell injury, whereas low (physiological) NO concentrations often ameliorate cell injury. We tested the hypotheses that pretreatment of endothelial cells with low concentrations of NO (preconditioning) would prevent injury induced by high NO concentrations. Apoptosis, induced in bovine aortic endothelial cells (BAECs) by exposing them to either 4 mM sodium nitroprusside (SNP) or 0.5 mM N-(2-aminoethyl)- N-(2-hydroxy-2-nitrosohydrazino)-1,2-ethylenediamine (spermine NONOate) for 8 h, was abolished by 24-h pretreatment with either 100 μM SNP, 10 μM spermine NONOate, or 100 μM 8-bromo-cGMP (8-Br-cGMP). Repair of BAECs following wounding, measured as the recovery rate of transendothelial electrical resistance, was delayed by 8-h exposure to 4 mM SNP, and this delay was significantly attenuated by 24-h pretreatment with 100 μM SNP. NO preconditioning produced increased association and expression of soluble guanyl cyclase (sGC) and heat shock protein 90 (HSP90). The protective effect of NO preconditioning, but not the injurious effect of 4 mM SNP, was abolished by either a sGC activity inhibitor 1H-[1,2,4]oxadiazolo-[4,3- a]quinoxalin-1-one (ODQ) or a HSP90 binding inhibitor (radicicol) and was mimicked by 8-Br-cGMP. We conclude that preconditioning with a low dose of NO donor accelerates repair and maintains endothelial integrity via a mechanism that includes the HSP90/sGC pathway. HSP90/sGC may thus play a role in the protective effects of NO-generating drugs from injurious stimuli.

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