Differentiating between effects of streptozotocin per se and subsequent hyperglycemia on renal function and metabolism in the streptozotocin-diabetic rat model.

The animal model with streptozotocin (STZ)-induced diabetes mellitus is associated with progressive renal disturbances. The aim of this study was to differentiate between toxic effects of STZ and the effect of hyperglycemia. Previous studies have been limited to investigating the influence of STZ on glomerular filtration rate (GFR), albuminuria and renal morphology. The present study presents a new approach when transplanting beta-cells to cure the STZ-treated animals and extends the evaluation to include both renal function and oxygen metabolism. Animals were allocated to three groups: control animals, STZ-diabetic animals and animals rendered diabetic with an injection of STZ, followed by immediate syngeneic transplantation of approximately 1000 pancreatic islets into the splenic parenchyma. This latter procedure reversed the hyperglycemia induced by STZ. Renal function was evaluated from GFR and urinary albumin and protein leakage, while regional renal blood flow was determined using a laser-Doppler technique and oxygen tension measured with Clark-type electrodes. In diabetic animals, GFR increased, renal oxygen tension decreased and renal hypertrophy occurred, along with urinary leakage of protein, including albumin. Early transplantation of pancreatic islets to STZ-treated animals prevented the development of all these changes, except for proteinuria. However, an analysis of urinary protein content revealed that albuminuria was preventable by islet transplantation. We conclude that the urinary protein leakage in this animal model is at least partly due to direct toxic effects of STZ, whereas the other renal changes investigated in this study are due to the long-term diabetic condition. Copyright 2004 John Wiley & Sons, Ltd.