Insulin resistance and hypertension: studies in transgenic hypertensive TGR(mREN-2)27 rats

The link between hyperinsulinemia and hypertension is imperfectly understood. Recently, a renin gene (the mouse DBA/REN-2d gene) has been transfected into rats, leading to high blood pressure in transgene-positive animals, TGR(mREN-2)27 rats. We tested whether heterozygous hypertensive TGR(mREN-2)27 rats presented evidence of insulin resistance in comparison with the parent strain of Sprague-Dawley rats. Despite their higher blood pressure (203 +/- 8 vs. 112 +/- 6 mmHg, P < 0.001), transgenic rats had normal fasting levels of plasma glucose, insulin, free fatty acids, and triglycerides and had normal fasting rates of hepatic glucose production (by [14C]glucose infusion). During a euglycemic hyperinsulinemic clamp (3 mU/min), stimulation of whole body glucose utilization was equivalent in transgenic and control animals (12.6 +/- 0.6 vs. 10.9 +/- 1.0 mg.min-1.kg-1, respectively). Likewise, suppression of hepatic glucose output by insulin was complete in both groups. The glucose utilization index (as measured by the 2-deoxy-D-[3H]glucose technique) was similar between transgenic and control animals in several skeletal muscles (soleus, extensor digitorum longus, tibialis, diaphragm, white and red quadriceps, and white and red gastrocnemius), in white adipose tissue (periovarian and inguinal), and in brown adipose tissue. We conclude that single gene hypertension does not alter whole body and individual tissue insulin sensitivity.