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J Appl Physiol (May 3, 2002). doi:10.1152/japplphysiol.00236.2002
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Articles in PresS, published online ahead of print May 3, 2002
J Appl Physiol, 10.1152/jap.00236.2002
Submitted on March 19, 2002
Accepted on April 30, 2002

Modulation of Insulin Resistance and Hypertension by Voluntary Exercise Training in the TG(mREN2)27 Rat

Tyson R Kinnick1, Erik B Youngblood1, Matthew P O'Keefe1, Vitoon Saengsirisuwan1, Mary K Teachey1, and Erik J Henriksen1*

1 Department of Physiology, University of Arizona, Tucson, AZ, USA

* To whom correspondence should be addressed. E-mail: ejhenrik{at}u.arizona.edu.

Hypertension is often accompanied by insulin resistance of skeletal muscle glucose transport. The male heterozygous TG(mREN2)27 rat, which harbors a mouse transgene for renin, displays local elevations in the renin-angiotensin system and exhibits markedly elevated systolic blood pressure (SBP). The present study was undertaken to characterize insulin-stimulated skeletal muscle glucose transport in male heterozygous TG(mREN2)27 rats, and to evaluate the effect of voluntary exercise training on SBP and skeletal muscle glucose transport. Compared to normotensive Sprague-Dawley rats, age- and weight-matched TG(mREN2)27 rats displayed a 53% elevation (P<0.05) in SBP, a 2-fold increase in plasma free fatty acid (FFA) levels, and an exaggerated insulin response during an oral glucose tolerance test (OGTT). Moreover, insulin-mediated glucose transport (2-deoxyglucose uptake) in isolated epitrochlearis and soleus muscles of TG(mREN2)27 animals was 33% and 43% less than in Sprague-Dawley controls. TG(mREN2)27 rats were allowed to run voluntarily for 6 wk, and achieved daily running distances of 6-7 km over the final 3 wk. Training was associated with a 36% increase in peak aerobic capacity and a 16% reduction in resting SBP. Fasting plasma insulin (21%) and FFA (34%) levels were reduced in the trained TG(mREN2)27 rats. Whole-body glucose tolerance was improved in the trained TG(mREN2)27 rats, and was associated with increases of 39% and 50% in insulin-mediated glucose transport in epitrochlearis and soleus muscles. Whole-muscle GLUT-4 protein was increased in the soleus (23%), but not in the epirtrochlearis, of the trained TG(mREN2)27 rats. These data indicate that the male heterozygous TG(mREN2)27 rat is a model of both hypertension and insulin resistance. Importantly, both of these defects can be beneficially modified by voluntary exercise training.




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