DOWN-REGULATION OF THE RENIN-ANGIOTENSIN SYSTEM IN STREPTOZOTOCIN-DIABETIC RATS

To determine if insulin has the ability to regulate components of the renin-angiotensin system, renin and angiotensinogen mRNA and plasma concentrations were determined in 4-wk streptozotocin (STZ)-diabetic rats. In another group of STZ-diabetic rats, replacement insulin therapy was given over the 4-wk period, and the above parameters were examined. In STZ-diabetic rats, there was a significant regression of white adipose tissue that was accompanied by an increase in the yield of RNA obtained. Changes in white adipose tissue were reversed by insulin replacement therapy in STZ-diabetic rats. There were no changes in brown adipose tissue weight or RNA yield in STZ-diabetic rats. Plasma renin activity (PRA) was significantly decreased in STZ-diabetic rats; however, plasma angiotensinogen concentration was not significantly affected by diabetes. PRA was restored to control levels in STZ-diabetic rats with insulin replacement. Kidney renin mRNA as well as liver, epididymal, and interscapular fat angiotensinogen mRNA were significantly decreased in STZ-diabetic rats. Renin and angiotensinogen mRNA were not significantly different from control in all tissues examined in STZ-diabetic rats with insulin replacement therapy. Results from this study suggest a downregulation of the renin-angiotensin system in 4-wk STZ-diabetic rats at the level of mRNA expression that is restored by replacement therapy with insulin; therefore, insulin may directly or indirectly regulate the renin-angiotensin system.