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Titolo:
Aldose reductase expression is induced by hyperglycemia in diabetic nephropathy
Autore:
Hodgkinson, AD; Sondergaard, KL; Yang, BM; Cross, DF; Millward, BA; Demaine, AG;
Indirizzi:
Univ Plymouth, Dept Mol Med, Plymouth PL4 8AA, Devon, England Univ Plymouth Plymouth Devon England PL4 8AA outh PL4 8AA, Devon, England
Titolo Testata:
KIDNEY INTERNATIONAL
fascicolo: 1, volume: 60, anno: 2001,
pagine: 211 - 218
SICI:
0085-2538(200107)60:1<211:AREIIB>2.0.ZU;2-C
Fonte:
ISI
Lingua:
ENG
Soggetto:
PIGMENT EPITHELIAL-CELLS; GENE; SUSCEPTIBILITY; COMPLICATIONS; GLUCOSE; POLYMORPHISM; RETINOPATHY; MELLITUS; ALLELE; TRANSPORTER;
Keywords:
sorbitol dehydrogenase; gene expression; blood sugar; type 1 diabetes; ALR2 gene;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
27
Recensione:
Indirizzi per estratti:
Indirizzo: Demaine, AG Room S5,ITTC Bldg,Tamar Sci Pk,Davy Rd, Plymouth PL6 8BX, Devon, England Room S5,ITTC Bldg,Tamar Sci Pk,Davy Rd Plymouth Devon England PL6 8BX
Citazione:
A.D. Hodgkinson et al., "Aldose reductase expression is induced by hyperglycemia in diabetic nephropathy", KIDNEY INT, 60(1), 2001, pp. 211-218

Abstract

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 acandidate 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) orsupplemented with 10 mmol/L D-glucose (moderate hyperglyemia) or 20 mmol/LD-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 inthe 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-riskgenotypes (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.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 25/11/20 alle ore 16:53:30