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.

Phospholipase C isozymes(PLCs) paly a central role in ligand-mediated signal transduction for cellular activity such as proliferation and differentiation. However, the biolog-ical significance of their molecules in carcinogenesis or tumor progression is not determined precisely yet.

Usnig PLC-γ1 specific antibody, we have examined the relative contents of PLC-γ1 in various types of human cancer tissue, by immunoblotting and imm-unohistochemistry techniques. Several oncogene studies and DNA ploidy sutdy were per-formed additionally insome tumors.

Most malignancy showed elevated contentesof PLC-γ1, especially in colorectal and breast cancer, whereas hepatocellular carcinoma revealed decreased expression pf PLC-γ1. onco-protein expression was correlated with PLC-γ1 expression in some tumors. In hepatocellular carcinoma, DNA ploidy has an influenc to PLC-γ1 expression in most of the cases.

In conclusion, alteration or imbalance of the PLC-γ1 mediated signal trans-duction may have a significant role in the devlelopment or progression of cancer. These findings not only have important implications for increasing our understanding of multistage car-cinogenesis but they also have an impact on strategies for diagnosis and theraly of cancers.