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10.1074/jbc.M116.719666 http://scihub22266oqcxt.onion/10.1074/jbc.M116.719666 C4865906!4865906!27002150     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 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       J+Biol+Chem 2016 ; 291 (20): 10562-70 Nephropedia Template TP {{tp|p=27002150|t=2016. Activation of the cAMP-PKA pathway Antagonizes Metformin Suppression of Hepatic Glucose Production* |pdf=|usr=}}{{27002150}} gab.com Text Activation of the cAMP-PKA pathway Antagonizes Metformin Suppression of Hepatic Glucose Production* JO: J Biol Chem http://www.kidney.de/pget.php?&tw=1&pmid=27002150 #FOAvip Metformin is the most commonly prescribed oral anti-diabetic agent worldwide. Surprisingly, about 35% of diabetic patients either lack or have a delayed response to metformin treatment, and many patients become less responsive to metformin over time. It remains unknown how metformin resistance or insensitivity occurs. Recently, we found that therapeutic metformin concentrations suppressed glucose production in primary hepatocytes through AMPK; activation of the cAMP-PKA pathway negatively regulates AMPK activity by phosphorylating AMPK? subunit at Ser-485, which in turn reduces AMPK activity. In this study, we find that metformin failed to suppress glucose production in primary hepatocytes with constitutively activated PKA and did not improve hyperglycemia in mice with hyperglucagonemia. Expression of the AMPK?1(S485A) mutant, which is unable to be phosphorylated by PKA, increased both AMPK? activation and the suppression of glucose production in primary hepatocytes treated with metformin. Intriguingly, salicylate/aspirin prevents the phosphorylation of AMPK? at Ser-485, blocks cAMP-PKA negative regulation of AMPK, and improves metformin resistance. We propose that aspirin/salicylate may augment metformin's hepatic action to suppress glucose production. Twit Text FOAVip Activation of the cAMP-PKA pathway Antagonizes Metformin Suppression of Hepatic Glucose Production* ????J Biol Chem http://www.kidney.de/pget.php?&tw=1&pmid=27002150 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=27002150 #FOAvip English Wikipedia <ref>{{Cite pmid|27002150}}</ref> Activation of the cAMP-PKA pathway Antagonizes Metformin Suppression of Hepatic Glucose Production* #MMPMID27002150 He L; Chang E; Peng J; An H; McMillin SM; Radovick S; Stratakis CA; Wondisford FE J Biol Chem 2016[May]; 291 (20): 10562-70 PMID27002150show ga Metformin is the most commonly prescribed oral anti-diabetic agent worldwide. Surprisingly, about 35% of diabetic patients either lack or have a delayed response to metformin treatment, and many patients become less responsive to metformin over time. It remains unknown how metformin resistance or insensitivity occurs. Recently, we found that therapeutic metformin concentrations suppressed glucose production in primary hepatocytes through AMPK; activation of the cAMP-PKA pathway negatively regulates AMPK activity by phosphorylating AMPK? subunit at Ser-485, which in turn reduces AMPK activity. In this study, we find that metformin failed to suppress glucose production in primary hepatocytes with constitutively activated PKA and did not improve hyperglycemia in mice with hyperglucagonemia. Expression of the AMPK?1(S485A) mutant, which is unable to be phosphorylated by PKA, increased both AMPK? activation and the suppression of glucose production in primary hepatocytes treated with metformin. Intriguingly, salicylate/aspirin prevents the phosphorylation of AMPK? at Ser-485, blocks cAMP-PKA negative regulation of AMPK, and improves metformin resistance. We propose that aspirin/salicylate may augment metformin's hepatic action to suppress glucose production. äActivation of the cAMP-PKA pathway Antagonizes Metformin Suppression o(epmc).pdf DeepDyve Pubget Overpricing