DIFFERENTIAL SHORT-TERM AND LONG-TERM EFFECTS OF INSULIN ON ANG-II ACTION IN HUMAN ADRENAL GLOMERULOSA CELLS

Insulin is known to modulate several functions in bovine adrenal cells , including steroidogenesis and growth. However, the role of insulin i n regulating aldosterone synthesis in human adrenal glomerulosa cells has not been studied. In the present studies, we have examined the acu te and chronic effects of insulin on angiotensin II (ANG II)-induced a ldosterone synthesis in cultured normal and adenomatous human adrenal glomerulosa cells. Short-term insulin treatment (1.5 h) resulted in in hibition of ANG II-induced aldosterone synthesis. In contrast, chronic treatment (30 h) resulted in potentiation of ANG II action. The 12-li poxygenase pathway of arachidonate metabolism has been shown to play a key role in ANG II-induced aldosterone synthesis. The acute inhibitor y effects of insulin were in part mediated by inhibition of the 12-lip oxygenase 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 a n important regulator of ANG II-induced aldosterone synthesis in the a drenal.