| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Department of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
2 Department of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA; Department of Physiology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA; Department of Biochemistry, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
* To whom correspondence should be addressed. E-mail: Lawrence.mandarino{at}asu.edu.
Oversupply and underutilization of lipid fuels is recognized widely to be strongly associated with insulin resistance in skeletal muscle. Recent attention has focused on the mechanisms underlying this effect, and defects in mitochondrial function have emerged as a potential player in this scheme. Because evidence indicates that lipid oversupply can produce abnormalities in extracellular matrix composition and matrix changes can affect the function of mitochondria, the present study was undertaken to determine whether muscle from insulin resistant nondiabetic obese subjects and patients with type 2 diabetes mellitus had increased collagen content. Compared to lean control subjects, obese and type 2 diabetic subjects had reduced muscle glucose uptake (P < 0.01) and decreased insulin stimulation of tyrosine phosphorylation of IRS-1 and its ability to associate with PI 3-kinase (P < 0.01 and P < 0.05). As assayed by total hydroxyproline content, collagen abundance was increased in muscle from not only type 2 diabetic patients but also nondiabetic obese subjects (0.26 ± 0.05, 0.57 ± 0.18, and 0.67 ± 0.20 µg/mg muscle wet weight, lean controls, obese nondiabetics, and type 2 diabetics, respectively), indicating that hyperglycemia itself could not be responsible for this effect. Immunofluorescence staining of muscle biopsies indicated that there was increased abundance of types I and III collagen. We conclude that changes in the composition of the extracellular matrix are a general characteristic of insulin resistant muscle.
This article has been cited by other articles:
|
|
 |
|
  D. K. Coletta, B. Balas, A. O. Chavez, M. Baig, M. Abdul-Ghani, S. R. Kashyap, F. Folli, D. Tripathy, L. J. Mandarino, J. E. Cornell, et al. Effect of acute physiological hyperinsulinemia on gene expression in human skeletal muscle in vivo Am J Physiol Endocrinol Metab, May 1, 2008; 294(5): E910 - E917. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. De Filippis, G. Alvarez, R. Berria, K. Cusi, S. Everman, C. Meyer, and L. J. Mandarino Insulin-resistant muscle is exercise resistant: evidence for reduced response of nuclear-encoded mitochondrial genes to exercise Am J Physiol Endocrinol Metab, March 1, 2008; 294(3): E607 - E614. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Consoli, E. Martelli, M. D'Adamo, R. Menghini, D. Arcelli, O. Porzio, A. Pandolfi, G. R. Pistolese, A. Consoli, R. Lauro, et al. Insulin Resistance Affects Gene Expression in Endothelium Arterioscler. Thromb. Vasc. Biol., February 1, 2008; 28(2): e7 - e9. [Full Text] [PDF]
|
|
|
|
 |
|
 M. Bajaj, R. Medina-Navarro, S. Suraamornkul, C. Meyer, R. A. DeFronzo, and L. J. Mandarino Paradoxical Changes in Muscle Gene Expression in Insulin-Resistant Subjects After Sustained Reduction in Plasma Free Fatty Acid Concentration Diabetes, March 1, 2007; 56(3): 743 - 752. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
