| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Applied Physiology & Kinesiology, University of Florida, Gainesville, Florida, United States
* To whom correspondence should be addressed. E-mail: dcriswell{at}hhp.ufl.edu.
Nitric oxide (NO) and 5'-AMP-activated protein kinase (AMPK) are involved in glucose transport and mitochondrial biogenesis in skeletal muscle. Here, we examined whether NO regulates the expression of the major glucose transporter in muscle (GLUT4), and whether it influences AMPK-induced upregulation of GLUT4. At low levels, the NO-donor, SNAP (1 and 10µM), significantly increased GLUT4 mRNA (~3-fold; P<0.05) in L6 myotubes, and co-treatment with the AMPK inhibitor, Compound C, ablated this effect. The cGMP analog 8-Br-cGMP (2mM) increased GLUT4 mRNA by ~50% (P<0.05). GLUT4 protein expression was elevated 40% by 2d treatment with 8-Br-cGMP, whereas 6d treatment with 10µM SNAP increased GLUT4 expression by 65%. Co-treatment of cultures with the guanylyl cyclase inhibitor, ODQ, prevented the SNAP-induced increase in GLUT4 protein. 10µM SNAP also induced significant phosphorylation of 
AMPK, ACC and translocation of p-AMPK to the nucleus. Further, L6 myotubes exposed to 5-aminoimidazole-4-carboxamide-1-
-D-ribofuranoside (AICAR) for 16 hours presented an ~9-fold increase in GLUT4 mRNA, whereas co-treatment with the non-isoform specific NOS inhibitor, N(G)-L-nitro-arginine methyl ester (L-NAME), prevented ~70% of this effect. In vivo, GLUT4 mRNA was increased 1.8-fold in the rat plantaris muscle 12h after AICAR injection, and this induction was reduced by ~50% in animals co-treated with the nNOS and iNOS selective inhibitor, 1-(2-trifluoromethyl-phenyl)-imidazole (TRIM). We conclude that in skeletal muscle NO increases GLUT4 expression via a cGMP- and AMPK-dependent mechanism. The data are consistent with a role for NO in the regulation of AMPK, possibly via control of cellular activity of AMPK kinases and/or AMPK phosphatases.
This article has been cited by other articles:
|
|
 |
|
  J. R. Gayen, M. Saberi, S. Schenk, N. Biswas, S. M. Vaingankar, W. W. Cheung, S. M. Najjar, D. T. O'Connor, G. Bandyopadhyay, and S. K. Mahata A Novel Pathway of Insulin Sensitivity in Chromogranin A Null Mice: A CRUCIAL ROLE FOR PANCREASTATIN IN GLUCOSE HOMEOSTASIS J. Biol. Chem., October 16, 2009; 284(42): 28498 - 28509. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Wehling-Henricks, M. Oltmann, C. Rinaldi, K. H. Myung, and J. G. Tidball Loss of positive allosteric interactions between neuronal nitric oxide synthase and phosphofructokinase contributes to defects in glycolysis and increased fatigability in muscular dystrophy Hum. Mol. Genet., September 15, 2009; 18(18): 3439 - 3451. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. F. Ndisang, N. Lane, and A. Jadhav Upregulation of the heme oxygenase system ameliorates postprandial and fasting hyperglycemia in type 2 diabetes Am J Physiol Endocrinol Metab, May 1, 2009; 296(5): E1029 - E1041. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Foller, M. Sopjani, S. Koka, S. Gu, H. Mahmud, K. Wang, E. Floride, E. Schleicher, E. Schulz, T. Munzel, et al. Regulation of erythrocyte survival by AMP-activated protein kinase FASEB J, April 1, 2009; 23(4): 1072 - 1080. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. F. Ndisang and A. Jadhav Heme oxygenase system enhances insulin sensitivity and glucose metabolism in streptozotocin-induced diabetes Am J Physiol Endocrinol Metab, April 1, 2009; 296(4): E829 - E841. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. A. Murphy, K. A. Fakira, Z. Song, A. Beuve, and V. H. Routh AMP-activated protein kinase and nitric oxide regulate the glucose sensitivity of ventromedial hypothalamic glucose-inhibited neurons Am J Physiol Cell Physiol, January 1, 2009; 297(3): C750 - C758. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Karnieli and M. Armoni Transcriptional regulation of the insulin-responsive glucose transporter GLUT4 gene: from physiology to pathology Am J Physiol Endocrinol Metab, July 1, 2008; 295(1): E38 - E45. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Drenning, V. A. Lira, C. G. Simmons, Q. A. Soltow, J. E. Sellman, and D. S. Criswell Nitric oxide facilitates NFAT-dependent transcription in mouse myotubes Am J Physiol Cell Physiol, April 1, 2008; 294(4): C1088 - C1095. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. J. Green, T. A. Duhamel, G. P. Holloway, J. W. Moule, D. W. Ranney, A. R. Tupling, and J. Ouyang Rapid upregulation of GLUT-4 and MCT-4 expression during 16 h of heavy intermittent cycle exercise Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2008; 294(2): R594 - R600. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
