| 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
(Affiliation: Department of Medical Sciences, Uppsala University, University Hospital, Uppsala, Sweden. jan.melin at medsci.uu.se)
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| Journal | Kidney international
(Kidney Int)
Vol. 61
Issue 4
Pg. 1383-92
(Apr 2002)
ISSN: 0085-2538 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)
|
