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Abstract

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 with normotensive Sprague-Dawley rats, TG(mREN2)27 rats displayed a 53% elevation (P < 0.05) in SBP, a twofold increase in plasma free fatty acid levels, and an exaggerated insulin response during an oral glucose tolerance test. Moreover, insulin-mediated glucose transport (2-deoxyglucose uptake) in isolated epitrochlearis and soleus muscles of TG(mREN2)27 animals was 33 and 43% less, respectively, than in Sprague-Dawley controls. TG(mREN2)27 rats ran voluntarily for 6 wk and achieved daily running distances of 6-7 km over the final 3 wk. Training caused a 36% increase in peak aerobic capacity and a 16% reduction in resting SBP. Fasting plasma insulin (21%) and free fatty acid (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, respectively. Whole muscle GLUT-4 protein was increased in the soleus (23%), but not in the epitrochlearis, of 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.