Insulin sensitivity, clearance and release in kininogen-deficient rats

Insulin sensitivity of kininogen-deficient rats was compared with that of n ormal rats using euglycaemic hyperinsulinaemic glucose clamping. Anaestheti zed animals were infused with 2-50 mU kg(-1) min(-1) of insulin and the glu cose infusion rates needed to maintain euglycaemia were determined. Maximum glucose uptake, insulin sensitivity index and insulin clearance were reduc ed in kininogen-deficient rats. Captopril increased the amount of glucose n eeded to maintain euglycaemia during infusion of 2 and 10 mU kg(-1) min(-1) of insulin in normal rats, but had no effect in kininoyen-deficient rats. Anaesthetized rats of both strains were given an intraperitoneal injection of glucose and the evolution of blood glucose was followed for 120 min, The peak increase was higher in kininogen-deficient rats. Similar larger incre ases in blood glucose were observed after glucose injection in normal rats previously treated with HOE 140, a bradykinin B-2, receptor antagonist. Aft er glucose injection, plasma insulin increased in both groups of rats but r eached lower levels in kininogen-deficient animals. These results suggest t hat bradykinin is involved not only in the clearance of glucose and insulin by the tissues during insulin infusion but also that bradykinin can affect the release of insulin after a glucose load.