Hepatocyte nuclear factors 1 alpha/4 alpha and forkhead box A2 regulate the solute carrier 2A2 (Slc2a2) gene expression in the liver and kidney of diabetic rats

Autor(es)

David-Silva, Aline ^[1] ; Freitas, Helayne S. ^[1] ; Okamoto, Maristela M. ^[1] ; Sabino-Silva, Robinson ^[2] ; Schaan, Beatriz D. ^{[3, 4]} ; Machado, Ubiratan F. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Dept Physiol & Biophys, Inst Biomed Sci, BR-05508000 Sao Paulo - Brazil

^[2] Fed Univ Alagoas UFAL, Inst Biol Sci & Hlth, Maceio - Brazil

^[3] Univ Fed Rio Grande do Sul, Dept Internal Med, Fac Med, Porto Alegre, RS - Brazil

^[4] Hosp Clin Porto Alegre, Div Endocrine, Porto Alegre, RS - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Life Sciences; v. 93, n. 22, p. 805-813, NOV 19 2013.
• Citações Web of Science: 17

Resumo

Aims: Solute carrier 2a2 (Slc2a2) gene codifies the glucose transporter GLUT2, a key protein for glucose flux in hepatocytes and renal epithelial cells of proximal tubule. In diabetes mellitus, hepatic and tubular glucose output has been related to Slc2a2/GLUT2 overexpression; and controlling the expression of this gene may be an important adjuvant way to improve glycemic homeostasis. Thus, the present study investigated transcriptional mechanisms involved in the diabetes-induced overexpression of the Slc2a2 gene. Main methods: Hepatocyte nuclear factors 1 alpha and 4 alpha (HNF-1 alpha and HNF-4 alpha), forkhead box A2 (FOXA2), sterol regulatory element binding protein-1c (SREBP-1c) and the CCAAT-enhancer-binding protein (C/EBP beta) mRNA expression (RT-PCR) and binding activity into the Slc2a2 promoter (electrophoretic mobility assay) were analyzed in the liver and kidney of diabetic and 6-day insulin-treated diabetic rats. Key findings: Slc2a2/GLUT2 expression increased by more than 50% (P<0.001) in the liver and kidney of diabetic rats, and 6-day insulin treatment restores these values to those observed in non-diabetic animals. Similarly, the mRNA expression and the binding activity of HNF-1 alpha, HNF-4 alpha and FOXA2 increased by 50 to 100% (P<0.05 to P<0.001), also returning to values of non-diabetic rats after insulin treatment. Neither the Srebf1 and Cebpb mRNA expression, nor the SREBP-1c and C/EBP-beta binding activity was altered in diabetic rats. Significance: HNF-1 alpha, HNF-4 alpha and FOXA2 transcriptional factors are involved in diabetes-induced overexpression of Slc2a2 gene in the liver and kidney. These data point out that these transcriptional factors are important targets to control GLUT2 expression in these tissues, which can contribute to glycemic homeostasis in diabetes. (C) 2013 Published by Elsevier Inc. (AU)

• Processo FAPESP: 12/04831-1 - Novos moduladores do controle glicêmico e do desenvolvimento de complicações crônicas no Diabetes mellitus: perspectivas preventivas e terapêuticas
• Beneficiário: Ubiratan Fabres Machado
• Linha de fomento: Auxílio à Pesquisa - Temático