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Jelkmann et al., Adv Exp Med Biol 2001 (Anemia) : HIF-1 DNA binding is also increased by insulin , and by interleukin-1 and tumor necrosis factor
Kietzmann et al., Blood 2003 (Anoxia) : Furthermore, insulin and the active PKB enhanced all 3 HIF alpha-subunit protein levels and HIF-1 DNA binding activity, as shown by electrophoretic mobility shift assays ( EMSAs )
Doronzo et al., Diabetologia 2006 (Insulin Resistance) : As it is not known whether the effects of insulin on VEGF involve activation of hypoxia-inducible factor-1 (HIF-1) , we aimed to evaluate : ( 1 ) whether insulin modulates HIF-1alpha protein synthesis and activity ; ( 2 ) the insulin signalling pathways involved ; and ( 3 ) the role of insulin resistance ... Using aortic VSMC taken from humans and Zucker rats and cultured in normoxia, the following were evaluated : ( 1 ) dose dependent ( 0.5, 1, 2 nmol/l ) and time dependent ( 2, 4, 6 h ) effects exerted by insulin on HIF-1alpha content in both nucleus and cytosol, measured by Western blots ; ( 2 ) insulin effects on HIF-1 DNA binding activity on the VEGF gene, measured by electrophoretic mobility shift assay ; and ( 3 ) involvement of the insulin signalling molecules in these insulin actions, by using the following inhibitors : LY294002 ( PI3-K ), PD98059 ( extracellular signal regulated kinase [ ERK ] ), SP600125 ( Jun N terminal kinase [ JNK ] ), SB203580 ( p38 mitogen activated protein kinase ) and rapamycin ( mammalian target of rapamycin ), and by detecting the insulin signalling molecules by Western blots
Biswas et al., Am J Physiol Heart Circ Physiol 2007 : Antioxidants DPI or apocynin completely blocked insulin stimulated HIF-1 activation ... Overall, our data provide strong evidence for the essential role of NADPH oxidase generated ROS in insulin stimulated activation of HIF-1
Glassford et al., Am J Physiol Endocrinol Metab 2007 : Hypoxia-inducible factor-1 (HIF-1) , a heterodimeric transcription factor involved in the angiogenic and metabolic responses to tissue hypoxia, has been shown to be activated by insulin in various settings
De Gasperi et al., Molecular neurodegeneration 2010 : In fibroblasts harboring the M146V Psen1 FAD mutation on a mouse Psen1 null background, metabolic induction of HIF-1a by insulin was impaired but not hypoxic induction by cobalt chloride ... Interestingly, in Psen1-/- primary neuronal cultures HIF-1a was induced normally in response to cobalt chloride but insulin induction of HIF-1a was impaired even though activation of the PI3K/Akt pathway by insulin proceeded normally in Psen1-/- neuronal cultures
Gao et al., J Pharmacol Exp Ther 2012 (Neovascularization, Pathologic...) : L-4F inhibited the expression and activity of HIF-1a induced by low oxygen concentration, cobalt chloride ( CoCl ( 2 ), a hypoxia-mimic compound ), lysophosphatidic acid, and insulin in two human ovarian cancer cell lines, OV2008 and CAOV-3
Meng et al., PloS one 2012 : NADPH oxidase 4 mediates insulin stimulated HIF-1a and VEGF expression, and angiogenesis in vitro ... Reactive oxygen species ( ROS ) have been shown to be involved in HIF-1a and VEGF expression induced by insulin , but the role of specific ROS sources has not been fully elucidated ... In this study we examined the role of NADPH oxidase subunit 4 (Nox4) in insulin stimulated HIF-1a and VEGF expression, and angiogenic responses in human microvascular endothelial cells ( HMVECs )
Biswas et al., PloS one 2013 : Here we show that insulin regulates HIF-1a by a novel transcriptional mechanism by a ROS-sensitive activation of Sp1 in 3T3-L1 preadipocyte ... Insulin shows little effect on HIF-1a protein stability, but increases HIF-1a promoter activity ... In summary, we reveal that insulin regulates HIF-1a by a novel transcriptional mechanism involving Sp1