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.
Melin
Jan
J
Department of Medical Sciences, Uppsala University, University Hospital, Uppsala, Sweden. jan.melin@medsci.uu.se
Hellberg
Olof
O
Larsson
Erik
E
Zezina
Lilian
L
Fellström
Bengt C
BC
D000818:Animals; D017209:Apoptosis; D003692:Delayed-Action Preparations; D003921:Diabetes Mellitus, Experimental; D003928:Diabetic Nephropathies / Q000473:pathology* / Q000503:physiopathology; D004334:Drug Administration Schedule; D020287:In Situ Nick-End Labeling; D007328:Insulin / Q000008:administration & dosage / Q000494:pharmacology*; D007511:Ischemia / Q000473:pathology* / Q000503:physiopathology; D007676:Kidney Failure, Chronic / Q000517:prevention & control; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012079:Renal Circulation; D015427:Reperfusion Injury / Q000473:pathology / Q000503:physiopathology
D003692:Delayed-Action Preparations; D007328:Insulin