AJP - Endocrinology and Metabolism, Vol 268, Issue 1 E100-E106, Copyright © 1995 by American Physiological Society
Differential short- and long-term effects of insulin on ANG II action in human adrenal glomerulosa cells
R. Natarajan, S. Kathuria, L. Lanting, N. Gonzales and J. Nadler
Department of Diabetes, Endocrinology and Metabolism, City of Hope National Medical Center, Duarte, California 91010.
Insulin is known to modulate several functions in bovine adrenal cells,
including steroidogenesis and growth. However, the role of insulin in
regulating aldosterone synthesis in human adrenal glomerulosa cells has not
been studied. In the present studies, we have examined the acute and
chronic effects of insulin on angiotensin II (ANG II)-induced aldosterone
synthesis in cultured normal and adenomatous human adrenal glomerulosa
cells. Short-term insulin treatment (1.5 h) resulted in inhibition of ANG
II-induced aldosterone synthesis. In contrast, chronic treatment (30 h)
resulted in potentiation of ANG II action. The 12-lipoxygenase pathway of
arachidonate metabolism has been shown to play a key role in ANG II-induced
aldosterone synthesis. The acute inhibitory effects of insulin were in part
mediated by inhibition of the 12-lipoxygenase pathway. The chronic
stimulatory effect of insulin seemed to be due at least in part to the
upregulation of cytochrome P-450 side-chain cleavage enzyme levels. These
findings suggest that insulin has a differential temporal effect on ANG II
action and therefore may be an important regulator of ANG II-induced
aldosterone synthesis in the adrenal.
