| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Department of Diabetes, Endocrinology, and Metabolism, City of Hope National Medical Center, Duarte, California 91010
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
ACKNOWLEDGEMENTS
FOOTNOTES
REFERENCES
ABSTRACT 
Balon, Thomas W., and Jerry L. Nadler. Evidence that
nitric oxide increases glucose transport in skeletal muscle.
J. Appl. Physiol. 82(1): 359-363, 1997.
Nitric oxide synthase (NOS) is expressed in skeletal muscle.
However, the role of nitric oxide (NO) in glucose transport in this
tissue remains unclear. To determine the role of NO in modulating
glucose transport, 2-deoxyglucose (2-DG) transport was measured in rat
extensor digitorum longus (EDL) muscles that were exposed to either a
maximally stimulating concentration of insulin or to an electrical
stimulation protocol, in the presence of
NG-monomethyl-L-arginine,
a NOS inhibitor. In addition, EDL preparations were exposed to sodium
nitroprusside (SNP), an NO donor, in the presence of submaximal and
maximally stimulating concentrations of insulin. NOS inhibition reduced
both basal and exercise-enhanced 2-DG transport but had no effect on
insulin-stimulated 2-DG transport. Furthermore, SNP increased 2-DG
transport in a dose-responsive manner. The effects of SNP and insulin
on 2-DG transport were additive when insulin was present in
physiological but not in pharmacological concentrations. Chronic
treadmill training increased protein expression of both type I and type
III NOS in soleus muscle homogenates. Our results suggest that NO may
be a potential mediator of exercise-induced glucose transport.
insulin; nitric oxide synthase isoforms; treadmill running; sodium
nitroprusside; 2-deoxyglucose transport
INTRODUCTION RECENT IMMUNOCYTOCHEMICAL STUDIES by Kobzik and
co-workers (8, 9) have noted that both the type I (neuronal) and type III (endothelial) isoforms of nitric oxide synthase (NOS) are expressed
in skeletal muscle. In conjunction with these findings, we have
observed that nitric oxide (NO) is released from incubated skeletal
muscle preparations (1). Furthermore, muscle NO release is augmented by
prior electrically induced contractions (1). Although the complete
physiological significance of NO in skeletal muscle remains to be
determined (17), a number of different researchers (8, 13-15) have
noted that NO may play a role in modulating contractile function.
A previous study (1) has demonstrated that incubation of skeletal
muscle with a NOS inhibitor decreased glucose transport (1). Both
insulin and exercise stimulate glucose transport utilization (5).
However, the potential role of NO in modulating glucose transport by
these stimuli is unknown. Accordingly, we designed experiments
utilizing both a NOS inhibitor and a NO donor to address the hypothesis
of whether NO is a potential mediator of either exercise-enhanced or
insulin-stimulated glucose transport.
Exercise protocols have been demonstrated to affect a number of
proteins within skeletal muscle (3). However, the effects of exercise
training on the expression of different NOS isoforms in skeletal muscle
have not been studied. Thus additional experiments were performed to
determine the effects of a chronic endurance-training protocol on NOS
protein expression in rat skeletal muscle.
These results indicate that NO might be a potential mediator of glucose
transport in skeletal muscle during the resting and postexercise state.
Furthermore, chronic exercise stimulates the protein expression of both
type I and type III NOS isoforms in soleus muscle.
MATERIALS AND METHODS
-2-ethanesulfonic acid, 1 mM EDTA, 1 mM ethylene glycol-bis(
-aminoethyl
ether)-N,N,N,N-tetraacetic acid, 1% Triton X-100, 0.1% sodium dodecyl sulfate (SDS), 2 mM dithiothreitol, and 1 µl/ml sodium vanadate by a polytron (Brinkmann, Westbury, NY) at a setting of 6 for 90 s. After homogenization, leupeptin (6 µl/ml), pepstatin A (1 µl/ml), and
phenylmethylsulfonyl fluoride (1 µl/ml) were added to the
homogenates, and tubes were placed on ice for 30 min. Homogenates were
centrifuged at 1,876 g for 3 min. The
resulting supernatants were assayed for protein by a dye-binding
procedure (Bio-Rad, Hercules, CA). The proteins were heated at 90°C
for 10 min in a water bath. Then 40 µg of protein from the soleus
muscles were separated by electrophoresis through a 6.5%
SDS-polyacrylamide gel. The gel was run at constant mA: 10 mA through a
stacking gel and 15 mA through the separating gel. Proteins were
transferred from the gel to polyvinylidene difluride membrane (Bio-Rad)
by using a Semiphor Semi-Dry transfer unit (Hoefer, San Francisco, CA).
The membranes were then washed with tris(hydroxymethyl)aminomethane
(Tris)-buffered saline-Tween 20 (TBST), consisting of 10 mM Tris (pH
7.5) with 100 mM NaCl and 0.1% Tween 20, for 5 min and were placed
into fresh TBST and allowed to incubate overnight at 4°C. A
Western-Light Chemiluminescent Detection System (Tropix, Bedford, MA)
was used in conjunction with primary antibodies for type I and type III
NOS isoforms (Transduction Laboratories, Lexington, KY). Rat brain and
human endothelial cell lysates were used as positive controls for type
I and type III NOS isoforms, respectively. After exposure to film,
densitometry was used for quantification.
Statistics.
All data are expressed as means ± SE. When two means were compared,
analysis was performed by an unpaired
t-test, except when the muscles were
taken from the contralateral leg for comparison with the opposite leg.
In this case, the paired t-test was
employed. When multiple means were compared, analyses were performed by an analysis of variance. If a significant
F ratio was found, further analysis
was performed by a Tukey's post hoc comparison.
P < 0.05 was selected for acceptance
of statistical significance.
RESULTS
2 M, SNP
significantly (P <0.01) decreased
2-DG transport to rate that was 75 ± 5% of that observed
in control incubations, which contained no SNP or insulin. SNP at a
concentration of 5 × 102 M resulted in an even
larger (50 ± 16%) reduction in 2-DG transport.
Figure 2 shows the effects of insulin and SNP alone and in combination with one another on 2-DG transport. Each agent, when used alone at the listed concentrations, has a significant (P < 0.05) submaximal effect on stimulating 2-DG transport. However, when used in combination at these submaximal stimulating concentrations with one another, there is an additive effect on the stimulation of 2-DG transport. When the muscles are exposed to a maximal stimulating concentration of insulin (20,000 µU/ml), SNP has no additional effect on the stimulation of 2-DG transport.
Effects of SNP on high-energy phosphate concentrations of skeletal muscle. SNP, when used at a concentration equal to or <10
2 M, did not alter
either ATP or CP concentrations of previously incubated EDL muscle
(results not shown). However, there was a significant decrease in ATP
(2.45 ± 0.21 vs. 5.26 ± 1.12 µmol/g) and CP (1.50 ± 0.22 vs. 14.51 ± 0.72 µmol/g) concentrations (both
n = 5;
P < 0.05) after incubation with 2 × 102 M SNP,
demonstrating that an incubation with a high concentration of SNP
compromises metabolic integrity of the muscle.
Effects of NOS inhibition on 2-DG transport.
Incubation with L-NMMA decreases
basal 2-DG by ~30% (Table 1, Fig.
3). In marked contrast,
L-NMMA has no effect on
insulin-stimulated 2-DG transport at either physiological (Fig. 3) or
pharmacological concentrations (Table 1). However, contraction-enhanced
2-DG transport is nearly completely abolished by NOS inhibition (Table 1).
|
||||||||||||||||||||||||
Effect of exercise training on NOS protein expression. Type I NOS protein is barely detectable in soleus muscle homogenates of sedentary rats (Fig. 4). However, soleus muscle obtained from trained rats shows a marked fourfold increase (P < 0.01) in type I NOS protein expression (4.09 ± 0.18 arbitrary units; n = 6) compared with their sedentary counterparts (1.00 ± 0.15 arbitrary units; n = 6). Type III NOS protein expression is also increased (P < 0.05) in soleus muscle samples obtained from trained rats (1.98 ± 0.40 arbitrary units; n = 6) compared with sedentary counterparts [1.00 ± 0.15 arbitrary units (n = 6)].
DISCUSSION
The major finding of the current studies is our observation that NOS inhibition selectively inhibits exercise enhanced 2-DG transport. Although it has been observed by ourselves (7, 21) and others (4, 5) that different factors activate glucose uptake in skeletal muscle, the signaling molecules or mechanisms remain obscure. Although further investigation is needed, we hypothesize that exercise activates glucose transport through a NO-mediated pathway, whereas insulin increases glucose-transport through a NO-independent mechanism.
Our finding that type I NOS protein can be increased by chronic endurance exercise is another example of a specific protein (i.e., GLUT-4 and hexokinase II) that has a key regulatory role in the control of glucose flux and can be upregulated by increased contractile activity (16, 20). These results support the potentially important regulatory role of specific NOS isoforms in exercise-induced improvement in glucose metabolism.
Our demonstration of increasing NOS protein expression of type I and type III isoforms by chronic endurance training extends the work of others (18) who have demonstrated that chronic exercise increases endothelial cell (type III) NOS gene expression in aortic extracts. It is possible that the increase in skeletal muscle NOS protein is a compensatory mechanism in response to the increase in metabolic demand.
Another major finding of these experiments that reinforces support for the role of NO in glucose transport regulation is that exposure to SNP, a NO donor, increases 2-DG transport in skeletal muscle over a wide range of concentrations. With high concentrations of SNP, 2-DG transport decreased. The stimulatory effects of SNP on glucose transport appear to be varied and dependent on the cell or tissue type examined. For example, Lander and associates (11) found that SNP, S-nitroso-N-acetylpenicillamine, or a NO gas-saturated medium increased glucose uptake in human peripheral blood mononuclear cells . Conversely, Emani and Perry (6) found that SNP had no stimulatory effect on glucose uptake in adipocytes. However, it should be noted that exposure to SNP did enhance triglyceride synthesis and protein synthesis in adipocytes, suggesting NO may selectively enhance certain insulin sensitive processes, depending on cell type (6). Furthermore, it should be noted that higher concentrations of SNP increased lactate dehydrogenase leakage from adipocytes, thus indicating a compromised metabolic integrity of the cell (6).
The concentration of SNP utilized in the majority of the current experiments was the same used by a number of other groups examining NO and skeletal muscle function (8, 13, 14). The aforementioned studies have noted that NO enhances force maintenance and is essential for optimal muscle function. These combined studies suggest that millimolar concentrations of SNP, when added for relatively short periods of times, are not detrimental to integrity of skeletal muscle metabolism.
In agreement with our prior investigation (1), we again demonstrated that NOS inhibition decreases basal glucose transport. However, NOS inhibition did not diminish 2-DG transport in skeletal muscle preparations by either submaximal or maximally stimulating concentrations of insulin. These results are somewhat different from those of Baron and co-workers (2), who observed insulin resistance after a bolus administration of L-NMMA, a NOS inhibitor. The disparity between studies most likely is because of the difference in the models utilized. We are examining skeletal muscle metabolism directly by using an incubated muscle preparation, whereas Baron et al. (2) examined whole body insulin responsiveness. Thus insulin in vivo may increase endothelial cell NO, resulting in vasodilatory responses and improved insulin responsiveness (19).
In conclusion, these new results suggest that modulation of the NO pathway in skeletal muscle could provide a novel approach to increasing glucose transport. Furthermore, the data indicate a potentially important role of NO in mediating exercise-induced glucose transport.
ACKNOWLEDGEMENTS
We thank Emilia Balon for technical assistance.
FOOTNOTES
Address for reprint requests: T. W. Balon, Dept. of Diabetes, Endocrinology and Metabolism, City of Hope National Medical Center, Duarte, CA 91010 (E-mail: TBALON{at}smtplink.coh.org).
Received 7 August 1996; accepted in final form 8 October 1996.
REFERENCES
| 1. |
Balon, T. W.,
and
J. L. Nadler.
Nitric oxide is present from incubated skeletal muscle preparations.
J. Appl. Physiol.
77:
2519-2521,
1994.
|
| 2. |
Baron, A. D.,
J.-S. Zhu,
S. Marshall,
O. Irsula,
G. Brechtel,
and
C. Keech.
Insulin resistance after hypertension induced by the nitric oxide synthesis inhibitor L-NMMA in rats.
Am. J. Physiol.
269:
E709-E715,
1995.
|
| 3. |
Booth, F. W.,
and
D. B. Thomason.
Molecular and cellular adaptation of muscle in responses to exercise: perspectives of various models.
Physiol. Rev.
71:
541-585,
1991.
|
| 4. |
Coderre, L.,
K. V. Kandror,
G. Vallega,
and
P. F. Pilch.
Identification and characterization of an exercise-sensitive pool of glucose transporters in skeletal muscle.
J. Biol. Chem.
270:
27584-27588,
1995.
|
| 5. |
Constable, S. H.,
R. J. Favier,
G. D. Cartee,
D. A. Young,
and
J. O. Holloszy.
Muscle glucose transport: interactions of in vitro contractions, insulin, and exercise.
J. Appl. Physiol.
64:
2329-2332,
1988.
|
| 6. | Emani, S., and M. C. Perry. A comparison of the effects of sodium and insulin on the control of metabolism in rat isolated adipocytes. Biochim. Biophys. Acta 804: 77-88, 1984. [Medline] |
| 7. |
Goodyear, L. J.,
F. Giorgino,
T. W. Balon,
G. Condorelli,
and
R. J. Smith.
Effects of contractile activity on tyrosine phosphoproteins of PI 3-kinase activity in rat skeletal muscle.
Am. J. Physiol.
268 (Endocrinol. Metab. 31):
E987-E995,
1995.
|
| 8. | Kobzik, L., M. B. Reid, D. S. Bredt, and J. S. Stamler. Nitric oxide in skeletal muscle. Nature Lond. 372: 546-548, 1994. [Medline] |
| 9. | Kobzik, L., B. Stringer, J.-L. Balligand, M. B. Reid, and J. S. Stamler. Endothelial type nitric oxide synthase in skeletal muscle fibers: mitochondrial relationships. Biochem. Biophys. Res. Commun. 211: 375-381, 1995. [Medline] |
| 10. | Lamprecht, W., and P. Stein. Creatine phosphate. In: Methods of Enzymatic Analysis, edited by H.-U. Bergmeyer. New York: Academic, 1965, p. 610-616. |
| 11. | Lander, H. M., P. Sehajpal, D. M. Levine, and A. Novogrodsky. Activation of human peripheral blood mononuclear cells by nitric oxide-generating compounds. J. Immunol. 150: 1509-1516, 1993. [Abstract] |
| 12. | Maizels, E. Z., N. B. Ruderman, M. N. Goodman, and D. Lau. Effect of acetoacetate on glucose metabolism in the soleus and extensor digitorum longus muscles of the rat. Biochem. J. 162: 557-568, 1977. [Medline] |
| 13. |
Morrison, R. J.,
C. C. Miller,
and
M. B. Reid.
Nitric oxide effects on shortening velocity and power production in the rat diaphragm.
J. Appl. Physiol.
80:
1065-1069,
1996.
|
| 14. | Murrant, C. L., and J. K. Barclay. Endothelial cell products alter mammalian skeletal muscle function in vitro. Can. J. Physiol. Pharmacol. 73: 736-741, 1995. [Medline] |
| 15. | Murrant, C. L., N. E. Woodley, and J. K. Barclay. Effect of nitroprusside and endothelium-derived products on slow-twitch skeletal muscle function in vitro. Can. J. Physiol. Pharmacol. 72: 1089-1093, 1994. [Medline] |
| 16. | Rodnick, K. J., J. O. Holloszy, C. E. Mondon, and D. E. James. Effects of exercise training on insulin-regulatable glucose-transporter protein levels in rat skeletal muscle. Diabetes 39: 1425-1429, 1990. [Abstract] |
| 17. |
Segal, S. S.
Invited editorial on "Nitric oxide release is present from incubated skeletal muscle preparations."
J. Appl. Physiol.
77:
2517-2518,
1994.
|
| 18. |
Sessa, W. C.,
K. Pritchard,
N. Seyedi,
J. Wang,
and
T. H. Hintze.
Chronic exercise in dogs increases coronary vascular nitric oxide production and endothelial cell nitric oxide synthase gene expression.
Circ. Res.
74:
349-353,
1994.
|
| 19. | Steinberg, H. O., G. Brechtel, A. Johnson, N. Fineberg, and A. D. Baron. Insulin-mediated skeletal muscle vasodilation is nitric oxide dependent. J. Clin. Invest. 94: 1172-1179, 1994. |
| 20. | Weber, F. E., and D. Pette. Contractile activity enhances the synthesis of hexokinase II in rat skeletal muscle. FEBS Lett. 238: 71-73, 1988. [Medline] |
| 21. |
Zorzano, A.,
T. W. Balon,
M. M. Goodman,
and
N. B. Goodman.
Additive effects of prior exercise and insulin on glucose and AIB uptake by rat muscle.
Am. J. Physiol.
251 (Endocrinol. Metab. 14):
E21-E26,
1986.
|
This article has been cited by other articles:
|
|
 |
|
  M. A. Chambers, J. S. Moylan, J. D. Smith, L. J. Goodyear, and M. B. Reid Stretch-stimulated glucose uptake in skeletal muscle is mediated by reactive oxygen species and p38 MAP-kinase J. Physiol., July 1, 2009; 587(13): 3363 - 3373. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Song, H.-B. Kwak, J.-H. Kim, and J. M. Lawler Exercise Training Modulates the Nitric Oxide Synthase Profile in Skeletal Muscle From Old Rats J Gerontol A Biol Sci Med Sci, May 1, 2009; 64A(5): 540 - 549. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. R. Pauli, E. R. Ropelle, D. E. Cintra, M. A. Carvalho-Filho, J. C. Moraes, C. T. De Souza, L. A. Velloso, J. B. C. Carvalheira, and M. J. A. Saad Acute physical exercise reverses S-nitrosation of the insulin receptor, insulin receptor substrate 1 and protein kinase B/Akt in diet-induced obese Wistar rats J. Physiol., January 15, 2008; 586(2): 659 - 671. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. M. Ross, G. D. Wadley, M. G. Clark, S. Rattigan, and G. K. McConell Local Nitric Oxide Synthase Inhibition Reduces Skeletal Muscle Glucose Uptake but Not Capillary Blood Flow During In Situ Muscle Contraction in Rats Diabetes, December 1, 2007; 56(12): 2885 - 2892. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. K. McConell, S. J. Bradley, T. J. Stephens, B. J. Canny, B. A. Kingwell, and R. S. Lee-Young Skeletal muscle nNOS{micro} protein content is increased by exercise training in humans Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2007; 293(2): R821 - R828. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Katz Modulation of glucose transport in skeletal muscle by reactive oxygen species J Appl Physiol, April 1, 2007; 102(4): 1671 - 1676. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Vassilakopoulos and S. N. A. Hussain Ventilatory muscle activation and inflammation: cytokines, reactive oxygen species, and nitric oxide J Appl Physiol, April 1, 2007; 102(4): 1687 - 1695. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Vassilakopoulos, K. Govindaraju, D. Parthenis, D. H. Eidelman, Y. Watanabe, and S. N. A. Hussain Nitric oxide production in the ventilatory muscles in response to acute resistive loading Am J Physiol Lung Cell Mol Physiol, April 1, 2007; 292(4): L1013 - L1022. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Nisoli, E. Clementi, M. O. Carruba, and S. Moncada Defective Mitochondrial Biogenesis: A Hallmark of the High Cardiovascular Risk in the Metabolic Syndrome? Circ. Res., March 30, 2007; 100(6): 795 - 806. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. D. Wadley and G. K. McConell Effect of nitric oxide synthase inhibition on mitochondrial biogenesis in rat skeletal muscle J Appl Physiol, January 1, 2007; 102(1): 314 - 320. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. L. Gonzalez-Sanchez, M. T. Martinez-Larrad, M. E. Saez, C. Zabena, M. J. Martinez-Calatrava, and M. Serrano-Rios Endothelial Nitric Oxide Synthase Haplotypes Are Associated with Features of Metabolic Syndrome Clin. Chem., January 1, 2007; 53(1): 91 - 97. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Sciorati, B. G. Galvez, S. Brunelli, E. Tagliafico, S. Ferrari, G. Cossu, and E. Clementi Ex vivo treatment with nitric oxide increases mesoangioblast therapeutic efficacy in muscular dystrophy J. Cell Sci., December 15, 2006; 119(24): 5114 - 5123. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. W. Balon Many pathways are called! Many may be chosen! J. Physiol., August 15, 2006; 575(1): 3 - 3. [Full Text] [PDF]
|
|
|
|
|
|
M. E. Sandstrom, S.-J. Zhang, J. Bruton, J. P. Silva, M. B. Reid, H. Westerblad, and A. Katz Role of reactive oxygen species in contraction-mediated glucose transport in mouse skeletal muscle J. Physiol., August 15, 2006; 575(1): 251 - 262. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. S. Stump, M. T. Hamilton, and J. R. Sowers Effect of Antihypertensive Agents on the Development of Type 2 Diabetes Mellitus Mayo Clin. Proc., June 1, 2006; 81(6): 796 - 806. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Pisconti, S. Brunelli, M. Di Padova, C. De Palma, D. Deponti, S. Baesso, V. Sartorelli, G. Cossu, and E. Clementi Follistatin induction by nitric oxide through cyclic GMP: a tightly regulated signaling pathway that controls myoblast fusion J. Cell Biol., January 17, 2006; 172(2): 233 - 244. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. K. McConell, N. N. Huynh, R. S. Lee-Young, B. J. Canny, and G. D. Wadley L-Arginine infusion increases glucose clearance during prolonged exercise in humans Am J Physiol Endocrinol Metab, January 1, 2006; 290(1): E60 - E66. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Abuissa, P. G. Jones, S. P. Marso, and J. H. O'Keefe Jr Angiotensin-Converting Enzyme Inhibitors or Angiotensin Receptor Blockers for Prevention of Type 2 Diabetes: A Meta-Analysis of Randomized Clinical Trials J. Am. Coll. Cardiol., September 6, 2005; 46(5): 821 - 826. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. W. Franks, J. Luan, I. Barroso, S. Brage, J. L. G. Sanchez, U. Ekelund, M. S. Rios, A. J. Schafer, S. O'Rahilly, and N. J. Wareham Variation in the eNOS Gene Modifies the Association Between Total Energy Expenditure and Glucose Intolerance Diabetes, September 1, 2005; 54(9): 2795 - 2801. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Suzuki Microvascular angioadaptation after endurance training with L-arginine supplementation in rat heart and hindleg muscles Exp Physiol, September 1, 2005; 90(5): 763 - 771. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. J. Rose and E. A. Richter Skeletal Muscle Glucose Uptake During Exercise: How is it Regulated? Physiology, August 1, 2005; 20(4): 260 - 270. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Jessen and L. J. Goodyear Contraction signaling to glucose transport in skeletal muscle J Appl Physiol, July 1, 2005; 99(1): 330 - 337. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Sydow, C. E Mondon, and J. P Cooke Insulin resistance: potential role of the endogenous nitric oxide synthase inhibitor ADMA Vascular Medicine, July 1, 2005; 10(1_suppl): S35 - S43. [Abstract] [PDF]
|
|
|
|
|
|
K. Sydow, C. E Mondon, and J. P Cooke Insulin resistance: potential role of the endogenous nitric oxide synthase inhibitor ADMA Vascular Medicine, May 1, 2005; 10(2_suppl): S35 - S43. [Abstract] [PDF]
|
|
|
|
 |
|
 S. R. Kashyap, L. J. Roman, J. Lamont, B. S. S. Masters, M. Bajaj, S. Suraamornkul, R. Belfort, R. Berria, D. L. Kellogg Jr., Y. Liu, et al. Insulin Resistance Is Associated with Impaired Nitric Oxide Synthase Activity in Skeletal Muscle of Type 2 Diabetic Subjects J. Clin. Endocrinol. Metab., February 1, 2005; 90(2): 1100 - 1105. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Qin, M. Nagasaki, M. Ren, G. Bajotto, Y. Oshida, and Y. Sato Gosha-jinki-gan (a Herbal Complex) Corrects Abnormal Insulin Signaling Evid. Based Complement. Altern. Med., December 1, 2004; 1(3): 269 - 276. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. J. Cottrell, R. D. Warner, M. B. McDonagh, and F. R. Dunshea Inhibition of endogenous nitric oxide production influences ovine hindlimb metabolism independently of insulin concentrations J Anim Sci, September 1, 2004; 82(9): 2558 - 2567. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Cook, O. Hugli, M. Egli, B. Menard, S. Thalmann, C. Sartori, C. Perrin, P. Nicod, B. Thorens, P. Vollenweider, et al. Partial Gene Deletion of Endothelial Nitric Oxide Synthase Predisposes to Exaggerated High-Fat Diet--Induced Insulin Resistance and Arterial Hypertension Diabetes, August 1, 2004; 53(8): 2067 - 2072. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. S. Zhang, W. E. Kraus, and G. A. Truskey Stretch-induced nitric oxide modulates mechanical properties of skeletal muscle cells Am J Physiol Cell Physiol, August 1, 2004; 287(2): C292 - C299. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Shearer, P. T. Fueger, B. Vorndick, D. P. Bracy, J. N. Rottman, J. A. Clanton, and D. H. Wasserman AMP Kinase-Induced Skeletal Muscle Glucose But Not Long-Chain Fatty Acid Uptake Is Dependent on Nitric Oxide Diabetes, June 1, 2004; 53(6): 1429 - 1435. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Bergandi, F. Silvagno, I. Russo, C. Riganti, G. Anfossi, E. Aldieri, D. Ghigo, M. Trovati, and A. Bosia Insulin Stimulates Glucose Transport Via Nitric Oxide/Cyclic GMP Pathway in Human Vascular Smooth Muscle Cells Arterioscler Thromb Vasc Biol, December 1, 2003; 23(12): 2215 - 2221. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Sato, M. Nagasaki, N. Nakai, and T. Fushimi Physical Exercise Improves Glucose Metabolism in Lifestyle-Related Diseases Experimental Biology and Medicine, November 1, 2003; 228(10): 1208 - 1212. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z.-P. Chen, T. J. Stephens, S. Murthy, B. J. Canny, M. Hargreaves, L. A. Witters, B. E. Kemp, and G. K. McConell Effect of Exercise Intensity on Skeletal Muscle AMPK Signaling in Humans Diabetes, September 1, 2003; 52(9): 2205 - 2212. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Vincent, E. J. Barrett, J. R. Lindner, M. G. Clark, and S. Rattigan Inhibiting NOS blocks microvascular recruitment and blunts muscle glucose uptake in response to insulin Am J Physiol Endocrinol Metab, July 1, 2003; 285(1): E123 - E129. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. J Fadel, W. Zhao, and G. D Thomas Impaired vasomodulation is associated with reduced neuronal nitric oxide synthase in skeletal muscle of ovariectomized rats J. Physiol., May 15, 2003; 549(1): 243 - 253. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. D. Thomas, P. W. Shaul, I. S. Yuhanna, S. C. Froehner, and M. E. Adams Vasomodulation by Skeletal Muscle-Derived Nitric Oxide Requires {alpha}-Syntrophin-Mediated Sarcolemmal Localization of Neuronal Nitric Oxide Synthase Circ. Res., March 21, 2003; 92(5): 554 - 560. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Vermes, A. Ducharme, M. G. Bourassa, M. Lessard, M. White, and J.-C. Tardif Enalapril Reduces the Incidence of Diabetes in Patients With Chronic Heart Failure: Insight From the Studies Of Left Ventricular Dysfunction (SOLVD) Circulation, March 11, 2003; 107(9): 1291 - 1296. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Vassilakopoulos, G. Deckman, M. Kebbewar, G. Rallis, R. Harfouche, and S. N. A. Hussain Regulation of nitric oxide production in limb and ventilatory muscles during chronic exercise training Am J Physiol Lung Cell Mol Physiol, March 1, 2003; 284(3): L452 - L457. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. C. Hickner, G. Kemeny, K. McIver, K. Harrison, and M. E. Hostetler Lower Skeletal Muscle Nutritive Blood Flow in Older Women Is Related to eNOS Protein Content J. Gerontol. A Biol. Sci. Med. Sci., January 1, 2003; 58(1): B20 - 25. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. J. Henriksen Exercise Effects of Muscle Insulin Signaling and Action: Invited Review: Effects of acute exercise and exercise training on insulin resistance J Appl Physiol, August 1, 2002; 93(2): 788 - 796. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. A. Kingwell, M. Formosa, M. Muhlmann, S. J. Bradley, and G. K. McConell Nitric Oxide Synthase Inhibition Reduces Glucose Uptake During Exercise in Individuals With Type 2 Diabetes More Than in Control Subjects Diabetes, August 1, 2002; 51(8): 2572 - 2580. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. N. Rottman, D. Bracy, C. Malabanan, Z. Yue, J. Clanton, and D. H. Wasserman Contrasting effects of exercise and NOS inhibition on tissue-specific fatty acid and glucose uptake in mice Am J Physiol Endocrinol Metab, July 1, 2002; 283(1): E116 - E123. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. I. McFarlane, R. Muniyappa, R. Francisco, and J. R. Sowers Pleiotropic Effects of Statins: Lipid Reduction and Beyond J. Clin. Endocrinol. Metab., April 1, 2002; 87(4): 1451 - 1458. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Piatti, L. D. Monti, G. Valsecchi, F. Magni, E. Setola, F. Marchesi, M. Galli-Kienle, G. Pozza, and K. G. M.M. Alberti Long-Term Oral L-Arginine Administration Improves Peripheral and Hepatic Insulin Sensitivity in Type 2 Diabetic Patients Diabetes Care, May 1, 2001; 24(5): 875 - 880. [Abstract] [Full Text]
|
|
|
|
 |
|
 G. D. Thomas, W. Zhang, and R. G. Victor Nitric Oxide Deficiency as a Cause of Clinical Hypertension: Promising New Drug Targets for Refractory Hypertension JAMA, April 25, 2001; 285(16): 2055 - 2057. [Full Text] [PDF]
|
|
|
|
 |
|
 T. Shiuchi, H. Nakagami, M. Iwai, Y. Takeda, T.-X. Cui, R. Chen, Y. Minokoshi, and M. Horiuchi Involvement of Bradykinin and Nitric Oxide in Leptin-Mediated Glucose Uptake in Skeletal Muscle Endocrinology, February 1, 2001; 142(2): 608 - 612. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Higaki, M. F. Hirshman, N. Fujii, and L. J. Goodyear Nitric Oxide Increases Glucose Uptake Through a Mechanism That Is Distinct From the Insulin and Contraction Pathways in Rat Skeletal Muscle Diabetes, February 1, 2001; 50(2): 241 - 247. [Abstract] [Full Text]
|
|
|
|
 |
|
 J. S. Stamler and G. Meissner Physiology of Nitric Oxide in Skeletal Muscle Physiol Rev, January 1, 2001; 81(1): 209 - 237. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. M. Fitzgerald and M. W. Brands Nitric oxide may be required to prevent hypertension at the onset of diabetes Am J Physiol Endocrinol Metab, October 1, 2000; 279(4): E762 - E768. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Tatchum-Talom, R. Schulz, J. R. McNeill, and F. H. Khadour Upregulation of neuronal nitric oxide synthase in skeletal muscle by swim training Am J Physiol Heart Circ Physiol, October 1, 2000; 279(4): H1757 - H1766. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. Frandsen, L. Hoffner, A. Betak, B. Saltin, J. Bangsbo, and Y. Hellsten Endurance training does not alter the level of neuronal nitric oxide synthase in human skeletal muscle J Appl Physiol, September 1, 2000; 89(3): 1033 - 1038. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. A. KINGWELL Nitric oxide-mediated metabolic regulation during exercise: effects of training in health and cardiovascular disease FASEB J, September 1, 2000; 14(12): 1685 - 1696. [Abstract] [Full Text]
|
|
|
|
|
|
D. Javeshghani, D. Sakkal, M. Mori, and S. N. A. Hussain Regulation of diaphragmatic nitric oxide synthase expression during hypobaric hypoxia Am J Physiol Lung Cell Mol Physiol, September 1, 2000; 279(3): L520 - L527. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. M A Heunks and P N R. Dekhuijzen Respiratory muscle function and free radicals: from cell to COPD Thorax, August 1, 2000; 55(8): 704 - 716. [Full Text]
|
|
|
|
|
|
W. Hirschfield, M. R. Moody, W. E. O'Brien, A. R. Gregg, R. M. Bryan Jr., and M. B. Reid Nitric oxide release and contractile properties of skeletal muscles from mice deficient in type III NOS Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2000; 278(1): R95 - R100. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. K. Roberts, R. J. Barnard, A. Jasman, and T. W. Balon Acute exercise increases nitric oxide synthase activity in skeletal muscle Am J Physiol Endocrinol Metab, August 1, 1999; 277(2): E390 - E394. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. J. Henriksen, S. Jacob, T. R. Kinnick, E. B. Youngblood, M. B. Schmit, and G. J. Dietze ACE inhibition and glucose transport in insulinresistant muscle: roles of bradykinin and nitric oxide Am J Physiol Regulatory Integrative Comp Physiol, July 1, 1999; 277(1): R332 - R336. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Zierler Whole body glucose metabolism Am J Physiol Endocrinol Metab, March 1, 1999; 276(3): E409 - E426. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Guo, M. T. Greenwood, B. J. Petrof, and S. N. A. Hussain Expression and Regulation of Protein Inhibitor of Neuronal Nitric Oxide Synthase in Ventilatory Muscles Am. J. Respir. Cell Mol. Biol., February 1, 1999; 20(2): 319 - 326. [Abstract] [Full Text]
|
|
|
|
 |
|
 M. P. Czech and S. Corvera Signaling Mechanisms That Regulate Glucose Transport J. Biol. Chem., January 22, 1999; 274(4): 1865 - 1868. [Full Text] [PDF]
|
|
|
|
 |
|
 D. S. Bredt NO skeletal muscle derived relaxing factor in Duchenne muscular dystrophy PNAS, December 8, 1998; 95(25): 14592 - 14593. [Full Text] [PDF]
|
|
|
|
|
|
Y. Fujii, Y. Guo, and S. N. A. Hussain Regulation of nitric oxide production in response to skeletal muscle activation J Appl Physiol, December 1, 1998; 85(6): 2330 - 2336. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. G. Tidball, E. Lavergne, K. S. Lau, M. J. Spencer, J. T. Stull, and M. Wehling Mechanical loading regulates NOS expression and activity in developing and adult skeletal muscle Am J Physiol Cell Physiol, July 1, 1998; 275(1): C260 - C266. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q. El Dwairi, Y. Guo, A. Comtois, E. Zhu, M. T. Greenwood, D. S. Bredt, and S. N. A. Hussain Ontogenesis of Nitric Oxide Synthases in the Ventilatory Muscles Am. J. Respir. Cell Mol. Biol., June 1, 1998; 18(6): 844 - 852. [Abstract] [Full Text]
|
|
|
|
|
|
D. Roy, M. Perreault, and A. Marette Insulin stimulation of glucose uptake in skeletal muscles and adipose tissues in vivo is NO dependent Am J Physiol Endocrinol Metab, April 1, 1998; 274(4): E692 - E699. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Hayashi, J. F. P. Wojtaszewski, and L. J. Goodyear Exercise regulation of glucose transport in skeletal muscle Am J Physiol Endocrinol Metab, December 1, 1997; 273(6): E1039 - E1051. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. W. Smith, J. D. Smith, and D. S. Criswell Involvement of nitric oxide synthase in skeletal muscle adaptation to chronic overload J Appl Physiol, May 1, 2002; 92(5): 2005 - 2011. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. J. Stephens, Z.-P. Chen, B. J. Canny, B. J. Michell, B. E. Kemp, and G. K. McConell Progressive increase in human skeletal muscle AMPKalpha 2 activity and ACC phosphorylation during exercise Am J Physiol Endocrinol Metab, March 1, 2002; 282(3): E688 - E694. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Iozzo, P. Chareonthaitawee, M. Di Terlizzi, D. J. Betteridge, E. Ferrannini, and P. G. Camici Regional myocardial blood flow and glucose utilization during fasting and physiological hyperinsulinemia in humans Am J Physiol Endocrinol Metab, May 1, 2002; 282(5): E1163 - E1171. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. M. Fitzgerald and M. W. Brands Hypertension in L-NAME-treated diabetic rats depends on an intact sympathetic nervous system Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2002; 282(4): R1070 - R1076. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
