AJP - Regulatory, Integrative and Comparative Physiology, Vol 267, Issue 6 1503-R1509, Copyright © 1994 by American Physiological Society
Insulin resistance and hypertension: studies in transgenic hypertensive TGR(mREN-2)27 rats
R. Vettor, I. Cusin, D. Ganten, F. Rohner-Jeanrenaud, E. Ferrannini and B. Jeanrenaud
Laboratoires de Recherches Metaboliques, Faculty of Medicine, University of Geneva, Switzerland.
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.
