Protective effect of insulin on ischemic renal injury in diabetes mellitus

Kidney Int. 2002 Apr;61(4):1383-92. doi: 10.1046/j.1523-1755.2002.00284.x.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Delayed-Action Preparations
  • Diabetes Mellitus, Experimental
  • Diabetic Nephropathies / pathology*
  • Diabetic Nephropathies / physiopathology
  • Drug Administration Schedule
  • In Situ Nick-End Labeling
  • Insulin / administration & dosage
  • Insulin / pharmacology*
  • Ischemia / pathology*
  • Ischemia / physiopathology
  • Kidney Failure, Chronic / prevention & control
  • Male
  • Rats
  • Rats, Wistar
  • Renal Circulation*
  • Reperfusion Injury / pathology
  • Reperfusion Injury / physiopathology

Substances

  • Delayed-Action Preparations
  • Insulin