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The current study reports that increasing hepatic PDC (show PDC Proteins) activity by inhibition of PDK2 ameliorates hepatic steatosis and insulin (show INS Proteins) sensitivity by regulating TCA cycle anaplerosis and ketogenesis. The findings suggest PDK2 is a potential therapeutic target for nonalcoholic fatty liver disease.
PDK2/4 induction and the subsequent lactate surge induce the metabolic shift in the diabetic dorsal root ganglion thereby contributing to the pathogenesis of painful diabetic neuropathy.
Double-knockout mice with global deletion of PDK2 and PDK4 (show PDK4 Proteins), which results in constitutively activated pyruvate dehydrogenase (show PDP Proteins), preferentially oxidize glucose in muscle.
The final compound of this series, 2-[(2,4-dihydroxyphenyl)sulfonyl]isoindoline-4,6-diol, designated PS10, inhibits all four PDK isoforms with IC50 = 0.8 muM for PDK2.
The Pdk4 (show PDK4 Proteins) gene knockdown led to better glucose tolerance than the Pdk2 gene knockdown.
loss of both Pdk2 and Pdk4 (show PDK4 Proteins) attenuated HSC (show FUT1 Proteins) quiescence, glycolysis, and transplantation capacity.
Results established that wild-type p53 (show TP53 Proteins) prevents manifestation of the Warburg effect by controlling Pdk2. These findings elucidate a new mechanism by which p53 (show TP53 Proteins) suppresses tumorigenesis acting at the level of cancer cell metabolism.
PDK2 activity is essential, even at rest, in regulation of carbohydrate oxidation and production of reducing equivalents for the electron transport chain.
mitochondrial ND2 mutation contributes to HIF1alpha (show HIF1A Proteins) accumulation via increased ROS (show ROS1 Proteins) production, up-regulation of PDK2, attenuating PDH (show PDP Proteins) activity, thereby increasing pyruvate, resulting in HIF1alpha (show HIF1A Proteins) stabilization
The data demonstrate potential roles of PDK2 and ABCG2 polymorphisms in the metabolic phenotypes of Tibetan gout patients.
High glycolysis and PDK2 overexpression are closely linked to cisplatin resistance in head and neck cancer cells, which can be reversed by PDK2 nhibition.
both PDK 1 (show PDK1 Proteins) and 2 isoforms are overexpressed in cutaneous melanoma compared to nevi, this expression being associated with the expression of the mTOR (show FRAP1 Proteins) pathway effectors and independent of the BRAF (show BRAF Proteins) mutational status
The findings of the present study reveal a novel survival pathway that functionally couples the unique glycolytic phenotype in cancer cells to hypoxia resistance via a PDK2-dependent mechanism that switches Bnip3 (show BNIP3 Proteins) from cell death to survival.
Germline mutations in PKD2 (show PKD2 Proteins) gene is associated with autosomal-dominant polycystic kidney disease.
we for the first time demonstrated that a low-nutrient condition drives cancer cells to utilize glycolysis to produce ATP, and this increases the Warburg effect through a novel mechanism involving ROS (show ROS1 Proteins)/AMPK (show PRKAA1 Proteins)-dependent activation of PDK.
Mitochondrial activation by inhibition of PDKII suppresses HIF1a (show HIF1A Proteins) signaling and angiogenesis in cancer.
Inactivation of pyruvate dehydrogenase kinase 2 by mitochondrial reactive oxygen species.
This gene encodes a member of the pyruvate dehydrogenase kinase family. The encoded protein phosphorylates pyruvate dehydrogenase, down-regulating the activity of the mitochondrial pyruvate dehydrogenase complex. Overexpression of this gene may play a role in both cancer and diabetes. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene.
pyruvate dehydrogenase kinase 2
, pyruvate dehydrogenase kinase, isoenzyme 2
, [Pyruvate dehydrogenase [lipoamide]] kinase isozyme 2, mitochondrial
, pyruvate dehydrogenase kinase, isozyme 2
, PDH kinase 2
, pyruvate dehydrogenase 2
, pyruvate dehydrogenase, lipoamide, kinase isozyme 2, mitochondrial
, PDK P45
, pyruvate dehydrogenase kinase 2 subunit p45 (PDK2)