Effect of insulin, proinsulin, and amylin on renin release from perfused rat kidney

Abstract To evaluate the possible role of insulin, proinsulin, and amylin in the renin-angiotensin system, the direct effect of these peptides on renin release was examined using perfused kidney of rats. Renin release was significantly increased from a basal value of 6.1 [plusmn] 1.8 to a peak value of 10.1 [plusmn] 2.3 ng angiotensin I (Ang I)/mL/h by 0.5 nmol insulin, from 6.0 [plusmn] 1.7 to 16.7 [plusmn] 4.5 ng Ang I/mL/h by 1 nmol insulin, and from 6.1 [plusmn] 1.8 to 18.0 [plusmn] 5.5 ng Ang I/mL/h by 8 nmol insulin. Renin release was not significantly changed by perfusion of 0.05 nmol proinsulin or amylin but significantly increased from a basal value of 6.1 [plusmn] 1.7 to a peak value of 8.1 [plusmn] 3.6 ng Ang I/mL/h by 1 nmol proinsulin, from 5.6 [plusmn] 1.7 to 12.1 [plusmn] 3.8 ng Ang I/mL/h by 8 nmol proinsulin, from 5.7 [plusmn] 1.9 to 8.2 [plusmn] 3.5 ng Ang I/mL/h by 1 nmol amylin, and from 5.2 [plusmn] 2.0 to 12.4 [plusmn] 3.3 ng Ang I/mL/h by 8 nmol amylin. The concentration of cyclic adenosine monophosphate in the effluent was significantly increased from a basal value of 5.1 [plusmn] 1.6 to a peak value of 10.6 [plusmn] 2.5 mmol/min by 8 nmol amylin but not altered by perfusion of insulin or proinsulin. The addition of 0.05 nmol proinsulin and 0.05 nmol of amylin on 0.5 nmol insulin significantly enhanced renin release. These results indicate that insulin may play an important physiologic role in the renin-angiotensin system and suggest that proinsulin and amylin may be involved in the genesis and development of hypertension through enhancement of insulin-stimulated renin release.