Protective effect of insulin on ischemic renal injury in diabetes mellitus

Background. An exceptional susceptibility to unilateral renal ischemia/reperfusion (I/R) injury resulting in inflammation, fibrosis, atrophy of the kidney, and end-stage renal disease (ESRD) has been demonstrated in the diabetic rat. The aim of this study was to examine whether insulin treatment would reduce I/R injury in diabetic kidneys. Methods. Diabetes mellitus (DM) was induced in male Wistar rats by streptozotocin. I/R was achieved by clamping the left renal artery for 30 minutes. Treatment with long acting insulin was started 7 to 14 days before or one day after I/R. Short acting insulin was administrated 2 to 6 hours before the injury. Apoptosis was evaluated six hours after ischemia with the TUNEL-method. Four weeks after the clamping inulin clearance was measured and kidneys were removed for histopathological evaluation. Results. In DM animals renal I/R caused massive induction of apoptosis in the renal medulla after six hours as well as inflammation, fibrosis, renal atrophy and anuria within four weeks. Treatment with long acting insulin before I/R resulted in decreased cell death and an almost complete protection of both renal function and histomorphology. Treatment with short acting, insulin before I/R also decreased the loss of renal function. In contrast, insulin treatment after I/R did not protect the kidney from damage. Conclusions. This study shows that insulin treatment with a subsequent improved metabolic control before renal I/R protected kidneys from ESRD.