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Induction of HIF normalizes oxygen utilization and oxygenation in the diabetic kidney
Author(s) -
Palm Fredrik,
Fasching Angelica,
Nangaku Masaomi,
Hansell Peter
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.812.11
Subject(s) - kidney , endocrinology , medicine , chemistry , diabetes mellitus , streptozotocin , renal function , oxygen , hypoxia (environmental) , organic chemistry
Hyperglycemia results in increased oxygen consumption (QO 2 ) and decreased oxygen tension (pO 2 ) in the kidney. We hypothesize that activation of hypoxia‐inducible factors (HIF) protect against diabetes‐induced alterations in kidney function and oxygen metabolism. The experimental groups consisted of control and streptozotocin‐induced diabetic rats with and without chronic cobalt chloride (CoCl 2 ; inducer of HIF; n=9–10/group). Diabetic rats had increased glomerular filtration rate (2.3±0.2 vs 1.5±0.2 ml/min/kidney; P<0.05) and CoCl 2 prevented this increase (1.5±0.1 ml/min/kidney). QO 2 was increased in the diabetic kidney (23±2 vs 11±2 μmol/min/kidney; P<0.05) and CoCl 2 prevented this alteration (12±2 μmol/min/kidney). Tubular sodium transport (T Na )/QO 2 was decreased in the diabetics (14±2 vs 33±8; P<0.05), which was prevented by CoCl 2 (25±4). Diabetic kidneys had reduced pO 2 in both cortex and medulla compared to control (29±1 vs 45±2 and 22±1 vs 30±1 mmHg, respectively; both P<0.05). CoCl 2 prevented these decreases (cortex 42±1; medulla 39±1 mmHg). All investigated parameters were unaltered by CoCl 2 in control rats. Diabetes‐induced alteration in kidney oxygen metabolism is prevented by HIF activation via two different mechanisms. Normalizing GFR, which reduces tubular electrolyte load, and maintaining T Na /QO 2 contribute to normal QO 2 and pO 2 in the diabetic kidney. Early pharmacological activation of the HIF system may prevent the development of diabetic nephropathy. Funding: NIH/NIDDK DK077858 and Swedish Research Council.