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10.1074/jbc.RA120.012533 http://scihub22266oqcxt.onion/10.1074/jbc.RA120.012533 31974165!7062158!31974165     free     free     free Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       J+Biol+Chem 2020 ; 295 (10): 3330-3346 Nephropedia Template TP {{tp|p=31974165|t=2020. Metformin lowers glucose 6-phosphate in hepatocytes by activation of glycolysis downstream of glucose phosphorylation |pdf=|usr=}}{{31974165}} gab.com Text Metformin lowers glucose 6-phosphate in hepatocytes by activation of glycolysis downstream of glucose phosphorylation JO: J Biol Chem http://www.kidney.de/pget.php?&tw=1&pmid=31974165 #FOAvip The chronic effects of metformin on liver gluconeogenesis involve repression of the G6pc gene, which is regulated by the carbohydrate-response element-binding protein through raised cellular intermediates of glucose metabolism. In this study we determined the candidate mechanisms by which metformin lowers glucose 6-phosphate (G6P) in mouse and rat hepatocytes challenged with high glucose or gluconeogenic precursors. Cell metformin loads in the therapeutic range lowered cell G6P but not ATP and decreased G6pc mRNA at high glucose. The G6P lowering by metformin was mimicked by a complex 1 inhibitor (rotenone) and an uncoupler (dinitrophenol) and by overexpression of mGPDH, which lowers glycerol 3-phosphate and G6P and also mimics the G6pc repression by metformin. In contrast, direct allosteric activators of AMPK (A-769662, 991, and C-13) had opposite effects from metformin on glycolysis, gluconeogenesis, and cell G6P. The G6P lowering by metformin, which also occurs in hepatocytes from AMPK knockout mice, is best explained by allosteric regulation of phosphofructokinase-1 and/or fructose bisphosphatase-1, as supported by increased metabolism of [3-(3)H]glucose relative to [2-(3)H]glucose; by an increase in the lactate m2/m1 isotopolog ratio from [1,2-(13)C(2)]glucose; by lowering of glycerol 3-phosphate an allosteric inhibitor of phosphofructokinase-1; and by marked G6P elevation by selective inhibition of phosphofructokinase-1; but not by a more reduced cytoplasmic NADH/NAD redox state. We conclude that therapeutically relevant doses of metformin lower G6P in hepatocytes challenged with high glucose by stimulation of glycolysis by an AMP-activated protein kinase-independent mechanism through changes in allosteric effectors of phosphofructokinase-1 and fructose bisphosphatase-1, including AMP, P(i), and glycerol 3-phosphate. Twit Text FOAVip Metformin lowers glucose 6-phosphate in hepatocytes by activation of glycolysis downstream of glucose phosphorylation ????J Biol Chem http://www.kidney.de/pget.php?&tw=1&pmid=31974165 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=31974165 #FOAvip English Wikipedia <ref>{{Cite pmid|31974165}}</ref> Metformin lowers glucose 6-phosphate in hepatocytes by activation of glycolysis downstream of glucose phosphorylation #MMPMID31974165 Moonira T; Chachra SS; Ford BE; Marin S; Alshawi A; Adam-Primus NS; Arden C; Al-Oanzi ZH; Foretz M; Viollet B; Cascante M; Agius L J Biol Chem 2020[Mar]; 295 (10): 3330-3346 PMID31974165show ga The chronic effects of metformin on liver gluconeogenesis involve repression of the G6pc gene, which is regulated by the carbohydrate-response element-binding protein through raised cellular intermediates of glucose metabolism. In this study we determined the candidate mechanisms by which metformin lowers glucose 6-phosphate (G6P) in mouse and rat hepatocytes challenged with high glucose or gluconeogenic precursors. Cell metformin loads in the therapeutic range lowered cell G6P but not ATP and decreased G6pc mRNA at high glucose. The G6P lowering by metformin was mimicked by a complex 1 inhibitor (rotenone) and an uncoupler (dinitrophenol) and by overexpression of mGPDH, which lowers glycerol 3-phosphate and G6P and also mimics the G6pc repression by metformin. In contrast, direct allosteric activators of AMPK (A-769662, 991, and C-13) had opposite effects from metformin on glycolysis, gluconeogenesis, and cell G6P. The G6P lowering by metformin, which also occurs in hepatocytes from AMPK knockout mice, is best explained by allosteric regulation of phosphofructokinase-1 and/or fructose bisphosphatase-1, as supported by increased metabolism of [3-(3)H]glucose relative to [2-(3)H]glucose; by an increase in the lactate m2/m1 isotopolog ratio from [1,2-(13)C(2)]glucose; by lowering of glycerol 3-phosphate an allosteric inhibitor of phosphofructokinase-1; and by marked G6P elevation by selective inhibition of phosphofructokinase-1; but not by a more reduced cytoplasmic NADH/NAD redox state. We conclude that therapeutically relevant doses of metformin lower G6P in hepatocytes challenged with high glucose by stimulation of glycolysis by an AMP-activated protein kinase-independent mechanism through changes in allosteric effectors of phosphofructokinase-1 and fructose bisphosphatase-1, including AMP, P(i), and glycerol 3-phosphate. |AMP-Activated Protein Kinases/deficiency/genetics[MESH] |Adenosine Triphosphate/metabolism[MESH] |Animals[MESH] |Dihydroxyacetone/pharmacology[MESH] |Gluconeogenesis/drug effects[MESH] |Glucose-6-Phosphate/*metabolism[MESH] |Glucose/*metabolism/pharmacology[MESH] |Glycerolphosphate Dehydrogenase/genetics/metabolism[MESH] |Glycolysis/*drug effects[MESH] |Hepatocytes/cytology/drug effects/metabolism[MESH] |Male[MESH] |Metformin/metabolism/*pharmacology[MESH] |Mice[MESH] |Mice, Inbred C57BL[MESH] |Mice, Knockout[MESH] |Phosphofructokinase-1/antagonists & inhibitors/metabolism[MESH] |Phosphorylation/drug effects[MESH] |Rats[MESH] |Rats, Wistar[MESH]Metformin lowers glucose 6-phosphate in hepatocytes by activation of g(epmc).pdf DeepDyve Pubget Overpricing