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 increased 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 determined by radiometric assay using [3H]-Hippuryl-glycyl-glycine as substrate. Fifteen days after onset of diabetes (n = 16), 8 rats received insulin daily (6-12 units/kg, s.c.) for 33 days, 8 diabetes rats remained untreated. Control, non-diabetic, rats (n = 8) received saline. The baseline serum ACE activity in the control group was 595 +/- 13 nmol/ml/min and did not change significantly throughout the study. However, serum 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 values. 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 untreated diabetic rats was increased by 46%, 47 days post-STZ. Insulin treatment reduced lung ACE activity to values similar to those observed in non-diabetic rats. These changes were associated with reduced kidney weight and urine volume. In summary, insulin administration to hyperglycaemic rats resulted in a reduction in the enhanced serum and lung ACE activity to values seen in non-diabetic rats. Normalizing the activity of the renin-angiotensin system may slow or prevent the glomerular hypertension, a major factor in the development of diabetic nephropathy.
Erman
A
A
Institute of Nephrology and Hypertension, Felsenstein Research Center, Rabin Medical Center (Beilinson Campus), Petah-Tikva, Israel.
Chen-Gal
B
B
David
I
I
Giler
S
S
Boner
G
G
van Dijk
D J
DJ
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001810:Blood Volume; D001835:Body Weight; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000201:enzymology* / Q000473:pathology; D007328:Insulin / Q000627:therapeutic use*; D007668:Kidney / Q000473:pathology; D008168:Lung / Q000201:enzymology*; D008297:Male; D009929:Organ Size; D007703:Peptidyl-Dipeptidase A / Q000097:blood* / Q000378:metabolism*; D010953:Plasma Volume; D051381:Rats; D017208:Rats, Wistar; D012083:Renin / Q000097:blood
D001786:Blood Glucose; D007328:Insulin; D007703:Peptidyl-Dipeptidase A; D012083:Renin