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PNDM is a genetically heterogeneous disorder due to mutations in 23 different genes described to date: KCNJ11, ABCC8, FOXP3, GCK, PDX1, pancreas-specific transcription factor 1A (PTF1A), EIF2AK3, SLC2A2, GATA6, GATA4, SLC19A2, WFS1, NEUROD1, NEUROG3, RFX6, LRBA, NKX2-2, MNX1, IER3IP1, INS, S T A T 3 , GLIS3 and HNF1B (3,4,5,6,7,8,9).
The SLC2A2 gene is a major glucose transporter in the cattle liver .
Carbohydrate regulators affected were insulin receptor substrate 2 (Irs2), glucose-responsive fork head box O1 (Foxo1), and glucose trans- porter 2 (Slc2a2).
Quantitative RT-PCR analyses of Insr and Slc2a2 genes were performed using TaqMan[TM] Fast Advanced Master Mix (Thermo Fisher Scientific 4444963) and TaqMan[R] Array Mouse Fatty Liver (Thermo Fisher Scientific 4391524, RAEPRZ3).
Gloyn, "GLUT2 (SLC2A2) is not the principal glucose transporter in human pancreatic beta cells: implications for understanding genetic association signals at this locus," Molecular Genetics and Metabolism, vol.
Brass et al .[sup] observed the amplification of genes BCHE and SLC2A2 at 3q26 in squamous cell lung carcinomas, whereas no amplification has been found in genes MME and KNG .
Compared with the blank control, mogrosides treatment showed no effect on the expression of the pyruvate kinase coding gene pklr, while palmitic acid significantly reduced expression of pklr (P<0.05; Figure 2A) and of the GLUT2 encoding gene slc2a2 in NIT-1 cells (P<0.05; Figure 2B).
Wilson et al., "Modeling of environmental effects in genome-wide association studies identifies SLC2A2 and HP as novel loci influencing serum cholesterol levels," PLoS Genetics, vol.
An initial 25 lead SNPs were followed up in 76 558 additional study participants, and 9 new loci were found to be associated (P < 5 x [10.sup.-8]) with fasting glucose (and/or HOMA-B) [adenylate cyclase 5 (ADCY5); MAP-kinase activating death domain (MADD); cryptochrome 2 (photolyase-like) (CRY2); adrenergic, alpha-2A-, receptor (ADRA2A); fatty acid desaturase 1 (FADS1); prospero homeobox 1 (PROX1); solute carrier family 2 (facilitated glucose transporter), member 2 (SLC2A2); GLIS family zinc finger 3 (GLIS3); and C2 calcium-dependent domain containing 4B (C2CD4B)] and 1 was found to be associated with fasting insulin and HOMA-IR concentrations [insulin-like growth factor 1 (somatomedin C) (IGF1)].
Following this, a next-generation sequencing assay was performed to analyze the coding regions and conserved splice sites of the 22 neonatal diabetes genes: KCNJ11, ABCC8, INS, EIF2AK3, FOXP3, GATA4, GATA6, GCK, GLIS3, HNF1B, IER3IP1, PDX1, PTF1A, NEUROD1, NEUROG3, NKX2-2, RFX6, SLC2A2, SLC19A2, STAT3, WFS1, and ZFP57 (Agilent custom capture v5.1/Illumina HiSeq) at the Molecular Genetics Laboratory, University of Exeter Medical School, UK (9).
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