Altered regulation of renin secretion by insulinlike growth factors and angiotensin II in diabetic rats.
The etiology of the low renin state in DM is not clear. To assess the role of certain growth and regulatory factors in this process, we studied the effects of insulin, IGF-I, and IGF-II on the renin-angiotensin system in normal and 8-wk STZ-induced diabetic rats. Renin secretion was studied both in static incubations and by perifusion of rat renal cortical slices. In diabetic rats, both plasma renin activity (0.65 +/- 1.6 vs. 4.0 +/- 1.2 ng ANG I.ml-1.h-1) and tissue renin concentrations (27 +/- 5 vs. 51 +/- 8 ng ANG I.mg tissue-1.h-1) were reduced. Insulin (0.1-1.0 mu/ml) and IGF-I (10(-9) to 4 x 10(-9) M) stimulated renin secretion in normal tissue (control, 95 +/- 3%; insulin [0.5 mu/ml], 134 +/- 7%; IGF-I [4 x 10(-9) M], 149 +/- 7%). IGF-I stimulated renin secretion in perifusions as early as 30 min, whereas IGF-II had no effect. However, in diabetic renal tissue, neither insulin (0.1-1.0 mu/ml) nor IGF-I (10(-9) to 4 x 10(-9) M) had an effect on renin. This lack of effect was overcome by adding up to 100-fold higher concentrations of these growth factors. ANG II (10(-10) M-10(-8) M) had an exaggerated inhibitory effect on renin secretion in diabetic tissue. This study suggests that the low renin state in DM may be explained by the enhanced inhibitory effect of ANG II and the resistance to the secretogogue actions of insulin and IGF-I.
Jost-Vu
E
E
University of Southern California Medical Center, Division of Endocrinology, Los Angeles 90033.
Horton
R
R
Antonipillai
I
I
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D007328:Insulin / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007335:Insulin-Like Growth Factor II / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012083:Renin / Q000378:metabolism*; D013311:Streptozocin
D007328:Insulin; D000804:Angiotensin II; D013311:Streptozocin; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D012083:Renin