Protective effect of insulin on ischemic renal injury in diabetes mellitus.

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.

• Authors: Jan Melin, Olof Hellberg, Erik Larsson, Lilian Zezina, Bengt C Fellström
• Journal: Kidney international (Kidney Int) Vol. 61 Issue 4 Pg. 1383-92 (Apr 2002) ISSN: 0085-2538 [Print] United States
• PMID: 11918745 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Delayed-Action Preparations
• Insulin

Topics

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