Tissue kallikrein and bradykinin do not have direct insulin-like actions on skeletal muscle glucose utilization.
Studies suggest that the actions of insulin on glucose metabolism may be mediated through activation of a membrane-bound serine protease with properties similar to a kallikrein-like enzyme. Also, bradykinin, a vasoactive product of kallikrein's action upon kininogen substrates, increases glucose uptake when infused into the human forearm. To determine whether a kallikrein or a kinin directly affects cellular glucose metabolism or participates in mediating insulin's actions, we studied their effects on isolated rat soleus muscle. Although trypsin (1.34 microM) increased incorporation of glucose into muscle glycogen to the same extent as insulin (200 mu units/ml), a purified rat tissue (urinary) kallikrein (0.4-1.34 microM) produced no such effect. Furthermore, the tissue kallikrein inhibitor, aprotinin, or a polyclonal kallikrein antiserum did not inhibit the action of insulin on incorporation of glucose into muscle glycogen. Treatment of the muscle preparation with bradykinin (1nM - 10 microM) did not result in any change in basal or insulin-stimulated (20 - 2000 mu units/ml) entry of glucose into glycogen or the glycolytic pathway. Bradykinin (1nM - 10 microM) also did not influence basal or insulin-stimulated (1000 mu units/ml) initial rates of glucose transport. These studies suggest that the previously observed in vivo effects of bradykinin on peripheral glucose uptake are probably mediated by changes in tissue perfusion rather than direct kinin effects on skeletal muscle, and that the putative membrane serine protease involved in the insulin-effector system is not tissue kallikrein.
Shimojo
N
N
Department of Medicine, Medical University of South Carolina, Charleston.
Pickens
T G
TG
Margolius
H S
HS
Mayfield
R K
RK
D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D003847:Deoxyglucose / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D006003:Glycogen / Q000378:metabolism; D006019:Glycolysis; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology*; D007610:Kallikreins / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D009132:Muscles / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D007328:Insulin; D006003:Glycogen; D003847:Deoxyglucose; D007610:Kallikreins; D005947:Glucose; D001920:Bradykinin