Decreased Angiotensin II -Stimulated Aldosterone Production, but Normal Inositol Phosphate Response in Adrenal Glomerulosa Cells from Streptozotocin-Induced Diabetic Rats: Role of lnsulin

Abstract

Streptozotocin(SlZ)-induced diabetic rats develop hyporeninemic hypoaldosteronism during the progression of diabetes mellitus. However,the nature and mechanism of aldosterone deficiency in diabetic rats still remain unclear and acute effects of insulin on aldosterone production in-vitro are not known. We evaluated the responses of aldosterone production to angiotensin 11 (AlI), potassium (K+), AClH and insulin in adrenal glomerulosa cells prepared from SlZ-induced diabetic rats with and without insulin treatment 2 weeks after diabetes induction. We also measured inositol phosphate<IP) levels in All-stimulated glomerulosa cells labeled with [3HI myoinositol using standardized anion exchange chromatography. Plasma renin activity and aldosterone level were not different among control rats,untreated and insulin-treated diabetic rats. Basal aldosterone production was similar in cells from the three groups. Cells from untreated diabetic rats showed a significant decrease in the maximal All (to-8M)-stimuiated aldosterone production and a tendency to be low in the maximal K+(8.7 mM)-stimulated aldosterone production, compared with control rats (3.2±2.2 \IS 7.7±2.4, P (0.05 and 4.8±1.8 \IS 8.0±3.2 ng/105 cells/hr, 0.05 (P (0.1, respectively). In contrast, there were no differences in All- and K+-stimulated aldosterone production between control and insulin-treated diabetic rats. AClH (to-8M), however, caused a similar effect on aldosterone production and insulin (I mU /ml for 1 hour) did not alter either basal or agonists-stimulated aldosterone production in cells from the three groups. All (to-8M)-induced IP formation among the three groups was similar and did not change with the addition of insulin u mU / ml), These results indicate that reduced response to All in the early phase of SlZ-induced diabetes in rats may be due to the zona glomerulosa dysfunction secondary to chronic lack of insulin and the main defect responsible for altered All effects may be located at some step(s) mediating All action downstream from IP formation.