The development of insulitis and the kallikrein-kinin system

Data derived from animals and humans suggest that the onset of diabetes is associated with hemodynamic changes in the renal circulation leading to increased renal plasma flow (RPF), glomerular capillary hyperfusion, and an increased glomerular transcapillary hydraulic pressure gradient. The duration of diabetes is one of the most important factors in predicting the development of diabetic nephropathy. On the other hand, diabetic nephropathy has been associated with the degree of hyperglycemia; thus, hyperglycemia may therefore contribute to alterations in structure and function of the kidney. In the present paper, we investigated early alterations of renal function in C57BL/KSJ mdb male mice that were injected with sub-diabetogenic doses of STZ. Urinary protein excretion (UPE) increased significantly at 12 and 18-20 days after STZ with a glucose level of 4-6 mm/l; the progressive increase of glycemia was followed by a progressive increase of UPE. In a similar way, urinary nitrite (NO2-) was also significantly increased. Urinary kallikrein excretion started to increase at a level of 4-6 mmol/l blood glucose concentration (BGC) 8 days after administration of STZ, and kidney vascular permeability also increased following the increment of BGC. These results confirm the presence of early modifications of renal function prior to the clinical detection of diabetic hyperglycemia.