HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 294/2/E345    most recent 00456.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wei, Y. Articles by Stump, C. S. Search for Related Content PubMed PubMed Citation Articles by Wei, Y. Articles by Stump, C. S.

Angiotensin II-induced skeletal muscle insulin resistance mediated by NF-B activation via NADPH oxidase

¹Department of Internal Medicine, University of Missouri-Columbia; ²Harry S. Truman Memorial Veterans Affairs Medical Center, Columbia, Missouri; ³Wake Forest University School of Medicine, Winston-Salem, North Carolina; ⁴Diabetes Research Program, Department of Medicine, University of Arizona; and ⁵Southern Arizona Veterans Affairs Health Care System, Tucson, Arizona

Submitted 16 July 2007 ; accepted in final form 7 December 2007

Reduced insulin sensitivity is a key factor in the pathogenesis of type 2 diabetes and hypertension. Skeletal muscle insulin resistance is particularly important for its major role in insulin-mediated glucose disposal. Angiotensin II (ANG II) is integral in regulating blood pressure and plays a role in the pathogenesis of hypertension. In addition, we have documented that ANG II-induced skeletal muscle insulin resistance is associated with generation of reactive oxygen species (ROS). However, the linkage between ROS and insulin resistance in skeletal muscle remains unclear. To explore potential mechanisms, we employed the transgenic TG(mRen2)27 (Ren-2) hypertensive rat, which harbors the mouse renin transgene and exhibits elevated tissue ANG II levels, and skeletal muscle cell culture. Compared with Sprague-Dawley normtensive control rats, Ren-2 skeletal muscle exhibited significantly increased oxidative stress, NF-B activation, and TNF- expression, which were attenuated by in vivo treatment with an angiotensin type 1 receptor blocker (valsartan) or SOD/catalase mimetic (tempol). Moreover, ANG II treatment of L6 myotubes induced NF-B activation and TNF- production and decreased insulin-stimulated Akt activation and GLUT-4 glucose transporter translocation to plasma membranes. These effects were markedly diminished by treatment of myotubes with valsartan, the antioxidant N-acetylcysteine, NADPH oxidase-inhibiting peptide (gp91 ds-tat), or NF-B inhibitor (MG-132). Similarly, NF-B p65 small interfering RNA reduced NF-B p65 subunit expression and nuclear translocation and TNF- production but improved insulin-stimulated phosphorylation (Ser⁴⁷³) of Akt and translocation of GLUT-4. These findings suggest that NF-B plays an important role in ANG II/ROS-induced skeletal muscle insulin resistance.

nuclear factor-B; reduced nicotinamide adenine dinucleotide phosphate; renin-angiotensin system; reactive oxygen species; TG(mRen2)27 rat; tumor necrosis factor-; angiotensin receptor blocker

This article has been cited by other articles:

				L. Lavie and P. Lavie Molecular mechanisms of cardiovascular disease in OSAHS: the oxidative stress link Eur. Respir. J., June 1, 2009; 33(6): 1467 - 1484. [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]

				S. S. Ghosh, H. D. Massey, R. Krieg, Z. A. Fazelbhoy, S. Ghosh, D. A. Sica, I. Fakhry, and T. W. B. Gehr Curcumin ameliorates renal failure in 5/6 nephrectomized rats: role of inflammation Am J Physiol Renal Physiol, May 1, 2009; 296(5): F1146 - F1157. [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]

				M. Mitsuishi, K. Miyashita, A. Muraki, and H. Itoh Angiotensin II Reduces Mitochondrial Content in Skeletal Muscle and Affects Glycemic Control Diabetes, March 1, 2009; 58(3): 710 - 717. [Abstract] [Full Text] [PDF]

				N. Bashan, J. Kovsan, I. Kachko, H. Ovadia, and A. Rudich Positive and Negative Regulation of Insulin Signaling by Reactive Oxygen and Nitrogen Species Physiol Rev, January 1, 2009; 89(1): 27 - 71. [Abstract] [Full Text] [PDF]

				Y. Wei, K. Chen, A. T. Whaley-Connell, C. S. Stump, J. A. Ibdah, and J. R. Sowers Skeletal muscle insulin resistance: role of inflammatory cytokines and reactive oxygen species Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2008; 294(3): R673 - R680. [Abstract] [Full Text] [PDF]