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10.1124/jpet.116.239087 http://scihub22266oqcxt.onion/10.1124/jpet.116.239087 C5363764!5363764!28123046     free     free     free Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 245.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 245.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 245.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 245.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 245.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 245.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 245.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 245.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       J+Pharmacol+Exp+Ther 2017 ; 361 (1): 29-38 Nephropedia Template TP {{tp|p=28123046|t=2017. PDE5 Inhibitor Tadalafil and Hydroxychloroquine Cotreatment Provides Synergistic Protection against Type 2 Diabetes and Myocardial Infarction in Mice |pdf=|usr=}}{{28123046}} gab.com Text PDE5 Inhibitor Tadalafil and Hydroxychloroquine Cotreatment Provides Synergistic Protection against Type 2 Diabetes and Myocardial Infarction in Mice JO: J Pharmacol Exp Ther http://www.kidney.de/pget.php?&tw=1&pmid=28123046 #FOAvip Diabetes is associated with a high risk for ischemic heart disease. We have previously shown that phosphodiesterase 5 inhibitor tadalafil (TAD) induces cardioprotection against ischemia/ reperfusion (I/R) injury in diabetic mice. Hydroxychloroquine (HCQ) is a widely used antimalarial and anti-inflammatory drug that has been reported to reduce hyperglycemia in diabetic patients. Therefore, we hypothesized that a combination of TAD and HCQ may induce synergistic cardioprotection in diabetes. We also investigated the role of insulin-Akt-mammalian target of rapamycin (mTOR) signaling, which regulates protein synthesis and cell survival. Adult male db/db mice were randomized to receive vehicle, TAD (6 mg/kg), HCQ (50 mg/kg), or TAD + HCQ daily by gastric gavage for 7 days. Hearts were isolated and subjected to 30-minute global ischemia, followed by 1-hour reperfusion in Langendorff mode. Cardiac function and myocardial infarct size were determined. Plasma glucose, insulin and lipid levels, and relevant pancreatic and cardiac protein markers were measured. Treatment with TAD + HCQ reduced myocardial infarct size (17.4% ± 4.3% vs. 37.8% ± 4.9% in control group, P < 0.05) and enhanced the production of ATP. The TAD + HCQ combination treatment also reduced fasting blood glucose, plasma free fatty acids, and triglyceride levels. Furthermore, TAD + HCQ increased plasma insulin levels (513 ± 73 vs. 232 ± 30 mU/liter, P < 0.05) with improved insulin sensitivity, larger pancreatic ?-cell area, and pancreas mass. Insulin-like growth factor-1 (IGF-1) levels were also elevated by TAD + HCQ (343 ± 14 vs. 262 ± 22 ng/ml, P < 0.05). The increased insulin/IGF-1 resulted in activation of downstream Akt/mTOR cellular survival pathway. These results suggest that combination treatment with TAD and HCQ could be a novel and readily translational pharmacotherapy for reducing cardiovascular risk factors and protecting against myocardial I/R injury in type 2 diabetes. Twit Text FOAVip PDE5 Inhibitor Tadalafil and Hydroxychloroquine Cotreatment Provides Synergistic Protection against Type 2 Diabetes and Myocardial Infarction in Mice ????J Pharmacol Exp Ther http://www.kidney.de/pget.php?&tw=1&pmid=28123046 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=28123046 #FOAvip English Wikipedia <ref>{{Cite pmid|28123046}}</ref> PDE5 Inhibitor Tadalafil and Hydroxychloroquine Cotreatment Provides Synergistic Protection against Type 2 Diabetes and Myocardial Infarction in Mice #MMPMID28123046 Wang R; Xi L; Kukreja RC J Pharmacol Exp Ther 2017[Apr]; 361 (1): 29-38 PMID28123046show ga Diabetes is associated with a high risk for ischemic heart disease. We have previously shown that phosphodiesterase 5 inhibitor tadalafil (TAD) induces cardioprotection against ischemia/ reperfusion (I/R) injury in diabetic mice. Hydroxychloroquine (HCQ) is a widely used antimalarial and anti-inflammatory drug that has been reported to reduce hyperglycemia in diabetic patients. Therefore, we hypothesized that a combination of TAD and HCQ may induce synergistic cardioprotection in diabetes. We also investigated the role of insulin-Akt-mammalian target of rapamycin (mTOR) signaling, which regulates protein synthesis and cell survival. Adult male db/db mice were randomized to receive vehicle, TAD (6 mg/kg), HCQ (50 mg/kg), or TAD + HCQ daily by gastric gavage for 7 days. Hearts were isolated and subjected to 30-minute global ischemia, followed by 1-hour reperfusion in Langendorff mode. Cardiac function and myocardial infarct size were determined. Plasma glucose, insulin and lipid levels, and relevant pancreatic and cardiac protein markers were measured. Treatment with TAD + HCQ reduced myocardial infarct size (17.4% ± 4.3% vs. 37.8% ± 4.9% in control group, P < 0.05) and enhanced the production of ATP. The TAD + HCQ combination treatment also reduced fasting blood glucose, plasma free fatty acids, and triglyceride levels. Furthermore, TAD + HCQ increased plasma insulin levels (513 ± 73 vs. 232 ± 30 mU/liter, P < 0.05) with improved insulin sensitivity, larger pancreatic ?-cell area, and pancreas mass. Insulin-like growth factor-1 (IGF-1) levels were also elevated by TAD + HCQ (343 ± 14 vs. 262 ± 22 ng/ml, P < 0.05). The increased insulin/IGF-1 resulted in activation of downstream Akt/mTOR cellular survival pathway. These results suggest that combination treatment with TAD and HCQ could be a novel and readily translational pharmacotherapy for reducing cardiovascular risk factors and protecting against myocardial I/R injury in type 2 diabetes. äPDE5 Inhibitor Tadalafil and Hydroxychloroquine Cotreatment Provides S(epmc).pdf DeepDyve Pubget Overpricing