Mechanism of Angiotensin 2-Stimulated Aldosterone Secretion in Adrenal Glomerulosa Cells of Diabetic Rats ; Normal Phospholipase Activity and Intracellular Calcium Mobilization.
- Author:
Yeon Ah SUNG
;
Nan Ho KYUNG
- Publication Type:Original Article
- Keywords:
Diabetes Mellitus;
Angiotensin II;
Aldosterone;
Phospholipase;
Protein kinase C
- MeSH:
Acidosis;
Adrenocorticotropic Hormone;
Aldosterone*;
Angiotensin II;
Angiotensins*;
Animals;
Arachidonic Acid;
Calcium*;
Diabetes Mellitus;
Humans;
Hyperkalemia;
Hypoaldosteronism;
Inositol;
Insulin;
Lysophospholipids;
Phospholipases A2;
Phospholipases*;
Plasma;
Protein Kinase C;
Rats*;
Renin;
Second Messenger Systems;
Streptozocin;
Type C Phospholipases;
Zona Glomerulosa*
- From:Journal of Korean Society of Endocrinology
1997;12(2):230-244
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
BACKGROUND: Diabetic patients develop hypoaldosteronism which frequently caused hyperkalemia and metabolic acidosis and diabetic hypoaldosteronism is associated with selective unresponsiveness of aldosterone to angiotensin A-II, but mechanism of defect in A-II stimulated aldosterone response still remain unclear. METHODS: To elucidate the mechanism of defect in A-II stimulated aldosterone response, author evaluated the responses of aldosterone production to A-II, K+, and ACTH in adrenal glomerulosa cells prepared from streptozotocin induced diabetic rats, Inositol triphosphate (IP3) generated by activation of phospholipase C (PLC) and arachidonic acid and lysophospholipids generated by activation of phospholipase A2 (PLA2) were measured in A-II stimulated glomerulosa cells. Radiocalcium efflux and aldosterone response to second messenger of A-II such as PLC, IP3, PLA, AA and protein kinase C activator, 12-o-tetradecanoylphorbol 13 acetate (TPA). RESULTS: 1. Plasma renin activity and aldosterone levels 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 (p0.05). 4. Aldosterone responses to PLC, IP3, AA and TPA were significantly decreased in glomerulosa cells from diabetic rats compared with control and insulin treated diabetic rats (p<0.05), but aldosterone response to PLA2 was similar among the three groups (p>0.05). 45Ca efflux to PLC, IP3 PLA2 and AA were similar among the three groups (p>0.05). CONCLUSION: These results suggested that decreased A-II-stimulated aldosterone response was present in glomerulosa cells from streptozotocin 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 after activation of phospholipase and increase of intracellular calcium, and activation of PKC, or distal to that could be one of the causative mechanism.
