The Angiotensin II-Stimulated Phospholipase Activity in Adrenal Glomerulose Cells of Diabetic Rats

Diabetic patients develop hypoaldosteronism which frequently caused hyperkalemia and metabolic acidosis and diabetic hypoaldosteronism is associated with selective unresponsiveness of aldosterone to angiotensin II(A II), but mechanism of defect in A II stimulated aldosterone response still remain unclear.

To elucidate the mechanism of defect in A II stimulated aldosterone response and whether the defect was corrected by insulin treatment. author evaluated the responses of aldosterone production to A II, K⁺ and ACTH. I also evaluated the products of phospholipase C(PLC) and phospholipase D(PLD) activation important for increase of intracellular calcium and protein kinase C activation after A II activation in adrenal glomerulosa cells prepared from streptozotocin induced diabetic rats.

Two weeks after induction of diabetes by streptozotocin, rats were sacrificed by decapitation. The aldosterone production to A II, K⁺ and ACTH was measured by RIA. Inositol triphosphate(IP₃) and diacylglycerol(DAG) generated by activation of PLC and phosphatidic acid(PA), phosphatidylethanol(PEt) and DAG generated by activation of PLD were measured by anion exchange column and thin layer chromatography.

1) Plasma renin activity and aldosterone level were not different among control rats, untreated and insulin treated diabetic rats.

2) basal, ACTH and K⁺-stimulated aldosterone production were similar in cells from the three groups(p>0.05), but A II stimulated aldosterone production was significantly decreased in cells from untreated diabetic rats compared with control and insulin treated diabetic rats(p<0.05).

3) A II-induced IP₃, PA, PEt and DAG generation was similar among the three groups(p>0.05).

These results suggested that decreased A II-stimulated aldosterone response was present in glomerulosa cells from strepzptocin induced diabetic rats and reversed by insulin treatments. The main defect of altered A II response of zona glomerulosa might be located in the step distal to the activation of phospholipase.