| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
K-NFB pathway in muscle does not cause insulin resistance
1 Diabetes and Obesity Program, Garvan Institute of Medical Research, Sydney, New South Wales, Australia
* To whom correspondence should be addressed. E-mail: mcleasby{at}rvc.ac.uk.
Insulin resistance of skeletal muscle is a major defect in obesity and type 2 diabetes. Insulin resistance has been associated with a chronic sub-clinical inflammatory state in epidemiological studies and specifically with activation of the Inhibitor 
-B kinase (IBK)- Nuclear factor -B (NFB) pathway. However it is unclear whether this pathway plays a role in mediating insulin resistance in muscle in vivo. We separately over-expressed the p65 sub-unit of NFB and IBK
in single muscles of rats using in vivo electrotransfer and compared the effects after one week versus paired contralateral control muscles. A 64% increase in p65 protein (p<0.001) was sufficient to cause muscle fibre atrophy but had no effect on glucose disposal or glycogen storage in muscle under hyperinsulinaemic-euglycaemic clamp conditions. Similarly a 650% increase in IBK expression (p<0.001) caused a significant reduction in Inhibitor -B protein but also had no effect on clamp glucose disposal after lipid infusion. In fact, IBK over-expression in particular caused increases in activating tyrosine phosphorylation of Insulin Receptor Substrate-1 (24%; p=0.02) and serine phosphorylation of Akt (23%; p<0.001), implying a moderate increase in flux through the insulin signalling cascade. Interestingly, p65 over-expression resulted in a negative feedback reduction of 36% in Toll-like Receptor (TLR)-2 (p=0.03) but not TLR-4 mRNA. In conclusion activation of the IBK-NFB pathway in muscle does not seem to be an important local mediator of insulin resistance.
This article has been cited by other articles:
|
|
 |
|
  K. C. Sourris, J. G. Lyons, M. P.J. de Courten, S. L. Dougherty, D. C. Henstridge, M. E. Cooper, M. Hage, A. Dart, B. A. Kingwell, J. M. Forbes, et al. c-Jun NH2-Terminal Kinase Activity in Subcutaneous Adipose Tissue but Not Nuclear Factor-{kappa}B Activity in Peripheral Blood Mononuclear Cells Is an Independent Determinant of Insulin Resistance in Healthy Individuals Diabetes, June 1, 2009; 58(6): 1259 - 1265. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D.-E. Lee, S. Kehlenbrink, H. Lee, M. Hawkins, and J. S. Yudkin Getting the message across: mechanisms of physiological cross talk by adipose tissue Am J Physiol Endocrinol Metab, June 1, 2009; 296(6): E1210 - E1229. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. R. Bruce, A. J. Hoy, N. Turner, M. J. Watt, T. L. Allen, K. Carpenter, G. J. Cooney, M. A. Febbraio, and E. W. Kraegen Overexpression of Carnitine Palmitoyltransferase-1 in Skeletal Muscle Is Sufficient to Enhance Fatty Acid Oxidation and Improve High-Fat Diet-Induced Insulin Resistance Diabetes, March 1, 2009; 58(3): 550 - 558. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Van Gammeren, J. S. Damrauer, R. W. Jackman, and S. C. Kandarian The I{kappa}B kinases IKK{alpha} and IKK{beta} are necessary and sufficient for skeletal muscle atrophy FASEB J, February 1, 2009; 23(2): 362 - 370. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. M Caricilli, P. H Nascimento, J. R Pauli, D. M L Tsukumo, L. A Velloso, J. B Carvalheira, and M. J A Saad Inhibition of toll-like receptor 2 expression improves insulin sensitivity and signaling in muscle and white adipose tissue of mice fed a high-fat diet J. Endocrinol., December 1, 2008; 199(3): 399 - 406. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
