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Sub-diabetogenic doses of streptozotocin (STZ) produce insulitis, β 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.

Kallikrein/kinin system; Diabetes Insulitis is an inflammatory state of the islet of Langerhans (Catanzaro et al., 1994). The inflamma- tory process is sustained by synthesis and release of a large number of humoral mediators, that, in turn, initiate a cascade of systemic and local effector molecules. Kinins have long been proposed as prominent inflammatory mediators in the pathogene- sis of several diseases (Sharma and Moshin, 1990; Sharma, 1991), because they can induce all the cardinal signs of inflammatory reactions. The present study was designed to evaluate the mechanisms of the endogenous kinins in the evolution of insulitis. Male C57BL/Ks mdb mice were injected with strep- tozotocin (STZ) for 5 consecutive days (40 mg/kg