ICEECE2012 Poster Presentations Diabetes (248 abstracts)
GABA A receptor gene regulatory networks in peripheral blood TCD4+, TCD8+ AND CD14+ cells of recently diagnosed type 1 diabetes mellitus
D. Rassi 1 , A. Evangelista 1 , D. Brum 1 , N. Deghaide 1 , M. Foss-Freitas 1 , M. Foss 1 , E. Sakamoto-Hojo 1 , C. Sanjeevi 2 , G. Passos 1 & E. Donadi 1
1University of SÐo Paulo, RibeirÐo Preto, Brazil; 2University of SÐo Paulo, RibeirÐo Preto, Brazil; 2Karolinska Institutet, Stokholm, Sweden.
Gamma-aminobutyric acid (GABA) is a major inhibitory neurotransmitter primarily produced by neurons and pancreatic beta cells. GABA functional receptors (GABR) are expressed in brain, pancreas and peripheral blood lymphomononuclear cells (PBMC). After evaluating the differential gene expression in PBMC of recently diagnosed type 1 diabetes mellitus patients (T1D), three GABRA networks were observed, modulating the expression dozen of genes. The study was conducted on T (CD4+ and CD8+) and monocyte (CD14+) cells obtained from 20 pre-pubertal patients and 20 age- and sex-matched healthy controls, using cDNA microarrays. Significant and differentially expressed genes, revealed using the SAM program, were studied for gene networks (GeneNetwork 1.2 algorithm). Three different GABR subunit class genes (alpha1, alpha6 and beta1) up-regulated the expression of the genes related to cell cycle (CNNB1-cyclin M1, STOM-stomatin), apoptosis control (FAS-TNF receptor superfamily, BAT3-HLA-B associated transcript 3), cellular receptor (IL1RAP- interleukin 1 receptor accessory protein, BCAP29-B cell receptor, IK cytokine-down-regulator of HLA II), complement control (CD93-C1q receptor), glucose metabolism (PFKFB2-6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2), insulin receptor (INSR), oncogenes (RHOG-ras homolog gene family, RAB6-member RAS oncogene family), ubiquitins (UBC-ubiquitin C, UBE2Z-ubiquitin-conjugating enzyme E2Z, UBR4-ubiquitin protein ligase E3 component n-recognin 4, and UBAP-ubiquitin associated protein 1), growth factor (COL6A2-collagen, alpha 2, FGF13-fibroblast growth factor 13, FGF9-Fibroblast growth factor 9) among others. Although the role of GABA in the pathogenesis of diabetes has not been established, some studies have shown that GABA down regulates many immune system functions. This study further reports that PBMC may reflect the ongoing diabetes pathogenesis, and further discriminates several other genes with potential interest for T1D.
Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.
Funding: This work was supported, however funding details unavailable.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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