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- Title
Aldose reductase expression is induced by hyperglycemia in diabetic nephropathy.
- Authors
Hodgkinson, Andrea D.; Søndergaard, Karen L.; Yang, Bingmei; Cross, Debbie F.; Millward, Beverley A.; Demaine, Andrew G.
- Abstract
Aldose reductase expression is induced by hyperglycemia in diabetic nephropathy. Background. Despite good metabolic control, many patients with type 1 diabetes still develop nephropathy, implicating a role for genetic factors. Recent studies examining the regulatory region of the aldose reductase (ALR2) gene, the rate-limiting enzyme of the polyol pathway, support its role as a candidate gene for nephropathy. Here we report the quantitation of ALR2, together with sorbitol dehydrogenase mRNA in the peripheral blood mononuclear cells (PBMCs) of type 1 diabetic patients with (N = 29) and without nephropathy (N = 11) following stimulation with high levels of d-glucose. Methods. PBMCs from patients and normal controls were cultured for five days with phytohemagglutinin in either normoglycemia (11 mmol/L d-glucose) or supplemented with 10 mmol/L d-glucose (moderate hyperglyemia) or 20 mmol/L d-glucose (hyperglycemia). The RNA was extracted and analyzed by ribonuclease protection assay. Results. ALR2 mRNA levels were significantly elevated with increasing d-glucose concentration (normal to hyperglycemic) in those patients with nephropathy (P < 0.0001). In marked contrast, in those without nephropathy and in the normal healthy controls, there was no change in mRNA expression. Furthermore, those patients with nephropathy and the Z–2/X susceptibility genotype had the greatest increase in ALR2 mRNA compared with those with low-risk genotypes (P < 0.007). Conclusion. These results show that patients with nephropathy exhibit marked disturbances in the expression of the enzyme components of the polyol pathway. Ultimately this leads to tissue damage and ischemia.
- Subjects
ALDOSE reductase; DIABETIC nephropathies
- Publication
Kidney International, 2001, Vol 60, Issue 1, p211
- ISSN
0085-2538
- Publication type
Article
- DOI
10.1046/j.1523-1755.2001.00788.x