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10 Mitochondrial dysfunction in diabetic nephropathy
  1. A N Malik,
  2. A Czajka
  1. Diabetes Research Group, School of Medicine, King's College London, London, UK


Introduction/hypothesis We found altered mitochondrial gene expression in diabetic GK rat kidneys, both nuclear and mitochondrial encoded mRNAs were upregulated in association with hyperglycemia.1 We postulated that the increased mitochondrial encoded mRNAs resulted from increased mitochondrial DNA content per cell as a result of hyperglycemia and that this could be involved in the pathogenesis of diabetic nephropathy.

Methodology Mitochondrial DNA content was determined as mitochondrial genome to nuclear genome (MT/N) ratio using real time quantitative PCR in diabetic rat kidneys, human glomerular mesangial cells cultured in high glucose and in peripheral blood from patients with Type 1 and Type 2 diabetes with and without nephropathy.2

Results Diabetic GK rat kidneys had a significantly higher Mt/N ratio compared to normoglycemic age-matched controls. Cultured human glomerular mesangial cells showed a >200% increase in Mt/N after just 4 days of growth in high glucose, suggesting that glucose can directly increase Mt/N. We also found significantly enhanced Mt/N in peripheral blood of T2DM patients with nephropathy when compared with diabetics with no nephropathy, or with healthy controls.3 We are currently testing the hypothesis that elevated Mt/N correlates with increased oxidative stress and expanding the patient study to include T1D and T2D patients.

Conclusions Our data suggest that renal and circulating Mt/N values are elevated in diabetes and that resulting mitochondrial dysfunction could be contributing to the pathogenesis of diabetic nephropathy through increased oxidative stress.

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