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10.1038/s41598-018-22081-7 http://scihub22266oqcxt.onion/10.1038/s41598-018-22081-7 C5826917!5826917 !29483571     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 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\29483571 .jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117       Sci+Rep 2018 ; 8 (1 ): 3660 Nephropedia Template TP {{tp|p=29483571 |t=2018. A small molecule inhibitor of Nicotinamide N-methyltransferase for the treatment of metabolic disorders |pdf=|usr=}}{{29483571 }} gab.com Text A small molecule inhibitor of Nicotinamide N-methyltransferase for the treatment of metabolic disorders JO: Sci Rep http://www.kidney.de/pget.php?&tw=1&pmid=29483571 #FOAvip Nicotinamide N-methyltransferase (NNMT) is a cytosolic enzyme that catalyzes the transfer of a methyl group from the co-factor S-adenosyl-L-methionine (SAM) onto the substrate, nicotinamide (NA) to form 1-methyl-nicotinamide (MNA). Higher NNMT expression and MNA concentrations have been associated with obesity and type-2 diabetes. Here we report a small molecule analog of NA, JBSNF-000088, that inhibits NNMT activity, reduces MNA levels and drives insulin sensitization, glucose modulation and body weight reduction in animal models of metabolic disease. In mice with high fat diet (HFD)-induced obesity, JBSNF-000088 treatment caused a reduction in body weight, improved insulin sensitivity and normalized glucose tolerance to the level of lean control mice. These effects were not seen in NNMT knockout mice on HFD, confirming specificity of JBSNF-000088. The compound also improved glucose handling in ob/ob and db/db mice albeit to a lesser extent and in the absence of weight loss. Co-crystal structure analysis revealed the presence of the N-methylated product of JBSNF-000088 bound to the NNMT protein. The N-methylated product was also detected in the plasma of mice treated with JBSNF-000088. Hence, JBSNF-000088 may act as a slow-turnover substrate analog, driving the observed metabolic benefits. Twit Text FOAVip A small molecule inhibitor of Nicotinamide N-methyltransferase for the treatment of metabolic disorders ????Sci Rep http://www.kidney.de/pget.php?&tw=1&pmid=29483571 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=29483571 #FOAvip English Wikipedia <ref>{{Cite pmid|29483571 }}</ref> A small molecule inhibitor of Nicotinamide N-methyltransferase for the treatment of metabolic disorders #MMPMID29483571 Kannt A ; Rajagopal S ; Kadnur SV ; Suresh J ; Bhamidipati RK ; Swaminathan S ; Hallur MS ; Kristam R ; Elvert R ; Czech J ; Pfenninger A ; Rudolph C ; Schreuder H ; Chandrasekar DV ; Mane VS ; Birudukota S ; Shaik S ; Zope BR ; Burri RR ; Anand NN ; Thakur MK ; Singh M ; Parveen R ; Kandan S ; Mullangi R ; Yura T ; Gosu R ; Ruf S ; Dhakshinamoorthy S Sci Rep 2018[Feb]; 8 (1 ): 3660 PMID29483571 show ga Nicotinamide N-methyltransferase (NNMT) is a cytosolic enzyme that catalyzes the transfer of a methyl group from the co-factor S-adenosyl-L-methionine (SAM) onto the substrate, nicotinamide (NA) to form 1-methyl-nicotinamide (MNA). Higher NNMT expression and MNA concentrations have been associated with obesity and type-2 diabetes. Here we report a small molecule analog of NA, JBSNF-000088, that inhibits NNMT activity, reduces MNA levels and drives insulin sensitization, glucose modulation and body weight reduction in animal models of metabolic disease. In mice with high fat diet (HFD)-induced obesity, JBSNF-000088 treatment caused a reduction in body weight, improved insulin sensitivity and normalized glucose tolerance to the level of lean control mice. These effects were not seen in NNMT knockout mice on HFD, confirming specificity of JBSNF-000088. The compound also improved glucose handling in ob/ob and db/db mice albeit to a lesser extent and in the absence of weight loss. Co-crystal structure analysis revealed the presence of the N-methylated product of JBSNF-000088 bound to the NNMT protein. The N-methylated product was also detected in the plasma of mice treated with JBSNF-000088. Hence, JBSNF-000088 may act as a slow-turnover substrate analog, driving the observed metabolic benefits. |Animals [MESH] |Body Weight/drug effects [MESH] |Diabetes Mellitus, Type 2/drug therapy/enzymology [MESH] |Diet, High-Fat/adverse effects [MESH] |Enzyme Inhibitors/*therapeutic use [MESH] |Male [MESH] |Metabolic Diseases/*drug therapy/*enzymology [MESH] |Mice [MESH] |Mice, Inbred C57BL [MESH]A small molecule inhibitor of Nicotinamide N-methyltransferase for the(epmc).pdf DeepDyve Pubget Overpricing