INSULIN-TREATMENT REDUCES THE INCREASED SERUM AND LUNG ANGIOTENSIN-CONVERTING ENZYME-ACTIVITY IN STREPTOZOTOCIN-INDUCED DIABETIC RATS

Serum and lung angiotensin-converting enzyme (ACE) activity is increas ed in the streptozotocin (STZ)-diabetic rat. In the present study, the effect of insulin treatment on this increased ACE activity in the STZ -diabetic rat was investigated. Serum and tissue ACE activity was dete rmined by radiometric assay using [H-3]-Hippuryl-glycyl-glycine as sub strate. Fifteen days after onset of diabetes (n=16), 8 rats received i nsulin daily (6-12 units/kg, s.c.) for 33 days, 8 diabetic rats remain ed untreated. Control, non-diabetic, rats (n=8) received saline. The b aseline serum ACE activity in the control group was 595+/-13 nmol/ml/m in and did not change significantly throughout the study. However, ser um ACE activity in the untreated diabetic rats increased significantly as of day 14 post-STZ (650+/-24 nmol/ml/min, p<0.001) compared to the corresponding values of the control group and compared to baseline va lues. Insulin administration to diabetic rats starting on day 15 post- STZ caused a gradual reduction in serum ACE activity to basal values, being (527+/-22 nmol/ml/min) at day 47. ACE activity in lungs of untre ated diabetic rats was increased by 46%, 47 days post-STZ. Insulin tre atment reduced lung ACE activity to values similar to those observed i n non-diabetic rats. These changes were associated with reduced kidney weight and urine volume. In summary, insulin administration to hyperg lycaemic rats resulted in a reduction in the enhanced serum and lung A CE activity to values seen in non-diabetic rats. Normalizing the activ ity of the renin-angiotensin system may slow or prevent the glomerular hypertension, a major factor in the development of diabetic nephropat hy.