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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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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]
Total Authors: 6
[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
Total Affiliations: 4
Document type: Journal article
Source: Life Sciences; v. 93, n. 22, p. 805-813, NOV 19 2013.
Web of Science Citations: 17

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)

FAPESP's process: 12/04831-1 - New players in glycemic control and chronic complications of Diabetes mellitus: preventive and therapeutic perspectives
Grantee:Ubiratan Fabres Machado
Support type: Research Projects - Thematic Grants