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This study investigates the roles of insulin, HIF1α, and metabolic pathways in knockout (KO) and wild-type (WT) mice. Key findings include altered lactate and NADPH levels in liver tissues, expression changes in glycolytic and TCA cycle genes in KO mouse embryonic fibroblasts (MEFs), and differential expression of gluconeogenesis genes in both MEFs and liver tissues. The interaction between WWOX and HIF1α was also examined under normoxic and hypoxic conditions, highlighting the complex regulatory networks involved in metabolism and hypoxia response.
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Insulin Pdx4 A WT KO Figure S1
A Lactate levels (mice) B NADPH levels (livers) P< 0.03 P< 0.009 Figure S2
Expression levels of glycolytic genes in KO MEFs A Expression levels of TCA cycle genes in KO MEFs B Figure S3
Expression levels of Pentose Phosphate Pathway genes (MEFs) Expression levels of Gluconeogenesis genes (MEFs) C D E Expression levels of Gluconeogenesis genes (livers) Figure S3
A HIF1α target genes expression (MCF7) B HIF1α target genes expression (MCF7) ** ** ** ** ** * * * ** C HRE-Luciferase Assay D HIF1α mRNA levels in skeletal muscles P< 0.001 P< 0.001 P< 0.09 P< 0.01 Figure S4
A NBDG-glucose uptake ** ** * ** B HIF1α target genes expression in WT treated mice C HIF1α target genes expression in KO treated mice ** ** Figure S5
Endogenous WWOX physically interacts with endogenous HIF1α B Normoxia (+MG 132) Hypoxia IP: Anti-HIFα Anti-HIFα Anti-IgG Anti-IgG Anti-wwox Anti-wwox Lysis Lysis HIFα-OH WWOX interacts physically with HIF1α via its first WW domain A Hypoxia MG132 Input HIFα GST SDR GST WW1+2 GST SDR GST WW1+2 Control GST WW1 GST WW1 GST WW2 Control GST WW2 LAMIN WWOX HIFα HSP90 GST Figure S6 Hypoxia Pull down MG132 GST SDR GST WW1+2 GST SDR GST WW1+2 Control GST WW1 GST WW2 Control GST WW1 GST WW2 HIFα GST