Effects of aprotinin on the kallikrein-kinin system in type I diabetes (insulitis).
Sub-diabetogenic doses of streptozotocin (STZ) produce insulitis, beta cell destruction and diabetes in mice. Since kinin have been proposed as an inflammatory mediator in several diseases, we decided to evaluate the role of the kallikrein-kinin system in the evolution of insulitis. Male C 57 BL/KsJ mdb mice were injected with STZ (40 mg/kg) for 5 consecutive d. Aprotinin (4000 KIU/d) was injected simultaneously with STZ during 10 d. Plasma and urine samples collected on day 15 were assayed for glucose concentration and proteins, nitrites and kallikrein. Diabetic mice showed hyperglycemia and increased diuresis, marked proteinuria, nitrites and kallikrein. Administration of aprotinin, a potent tissue kallikrein inhibitor, to STZ mice, reduced the hyperglycemia and the altered renal function of the diabetic mice to level no different from normal mice. The present studies are consistent with the hypothesis that the over-production of tissue kallikrein in insulitis could be controlled by the effect of aprotinin.
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PROSIVAD-CONICET, Depto. of Physiology, Fac. Pharmacy and Biochemistry, Buenos Aires, Argentina.
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D000818:Animals; D007611:Aprotinin / Q000494:pharmacology*; D001786:Blood Glucose / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology; D006943:Hyperglycemia / Q000188:drug therapy / Q000201:enzymology; D016234:Kallikrein-Kinin System / Q000187:drug effects*; D007610:Kallikreins / Q000037:antagonists & inhibitors; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology*
D001786:Blood Glucose; D015842:Serine Proteinase Inhibitors; D007611:Aprotinin; D007610:Kallikreins