The Experts below are selected from a list of 55617 Experts worldwide ranked by ideXlab platform
Eun Seok Kang - One of the best experts on this subject based on the ideXlab platform.
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chronic hmgcr hmg coa reductase inhibitor treatment contributes to dysglycemia by upregulating hepatic gluconeogenesis through autophagy induction
Autophagy, 2015Co-Authors: Hye Jin Wang, Jae Yeo Park, Obin Kwon, Eun Yeong Choe, Eun Seok KangAbstract:Statins (HMGCR/HMG-CoA reductase [3-hydroxy-3-methylglutaryl-CoA reductase] inhibitors) are widely used to lower blood cholesterol levels but have been shown to increase the risk of type 2 diabetes mellitus. However, the molecular mechanism underlying diabetogenic effects remains to be elucidated. Here we show that Statins significantly increase the expression of key gluconeogenic enzymes (such as G6PC [glucose-6-phosphatase] and PCK1 (phosphoenolpyruvate carboxykinase 1 [soluble]) in vitro and in vivo and promote hepatic glucose output. Statin treatment activates autophagic flux in HepG2 cells. Acute suppression of autophagy with lysosome inhibitors in statin treated HepG2 cells reduced gluconeogenic enzymes expression and glucose output. Importantly, the ability of Statins to increase gluconeogenesis was impaired when ATG7 was deficient and BECN1 was absent, suggesting that autophagy plays a critical role in the diabetogenic effects of Statins. Moreover autophagic vacuoles and gluconeogenic genes expression in the liver of diet-induced obese mice were increased by Statins, ultimately leading to elevated hepatic glucose production, hyperglycemia, and insulin resistance. Together, these data demonstrate that chronic statin therapy results in insulin resistance through the activation of hepatic gluconeogenesis, which is tightly coupled to hepatic autophagy. These data further contribute to a better understanding of the diabetogenic effects of stains in the context of insulin resistance.
Hye Jin Wang - One of the best experts on this subject based on the ideXlab platform.
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Chronic HMGCR/HMG-CoA reductase inhibitor treatment contributes to dysglycemia by upregulating hepatic gluconeogenesis through autophagy induction
2018Co-Authors: Hye Jin Wang, Jae Yeo Park, Obin Kwon, Eun Yeong Choe, Chul Hoon Kim, Kyu Yeon Hur, Myung-shik Lee, Mijin Yun, Bong Soo Cha, Young-bum KimAbstract:Statins (HMGCR/HMG-CoA reductase [3-hydroxy-3-methylglutaryl-CoA reductase] inhibitors) are widely used to lower blood cholesterol levels but have been shown to increase the risk of type 2 diabetes mellitus. However, the molecular mechanism underlying diabetogenic effects remains to be elucidated. Here we show that Statins significantly increase the expression of key gluconeogenic enzymes (such as G6PC [glucose-6-phosphatase] and PCK1 (phosphoenolpyruvate carboxykinase 1 [soluble]) in vitro and in vivo and promote hepatic glucose output. Statin treatment activates autophagic flux in HepG2 cells. Acute suppression of autophagy with lysosome inhibitors in statin treated HepG2 cells reduced gluconeogenic enzymes expression and glucose output. Importantly, the ability of Statins to increase gluconeogenesis was impaired when ATG7 was deficient and BECN1 was absent, suggesting that autophagy plays a critical role in the diabetogenic effects of Statins. Moreover autophagic vacuoles and gluconeogenic genes expression in the liver of diet-induced obese mice were increased by Statins, ultimately leading to elevated hepatic glucose production, hyperglycemia, and insulin resistance. Together, these data demonstrate that chronic statin therapy results in insulin resistance through the activation of hepatic gluconeogenesis, which is tightly coupled to hepatic autophagy. These data further contribute to a better understanding of the diabetogenic effects of stains in the context of insulin resistance.
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chronic hmgcr hmg coa reductase inhibitor treatment contributes to dysglycemia by upregulating hepatic gluconeogenesis through autophagy induction
Autophagy, 2015Co-Authors: Hye Jin Wang, Jae Yeo Park, Obin Kwon, Eun Yeong Choe, Eun Seok KangAbstract:Statins (HMGCR/HMG-CoA reductase [3-hydroxy-3-methylglutaryl-CoA reductase] inhibitors) are widely used to lower blood cholesterol levels but have been shown to increase the risk of type 2 diabetes mellitus. However, the molecular mechanism underlying diabetogenic effects remains to be elucidated. Here we show that Statins significantly increase the expression of key gluconeogenic enzymes (such as G6PC [glucose-6-phosphatase] and PCK1 (phosphoenolpyruvate carboxykinase 1 [soluble]) in vitro and in vivo and promote hepatic glucose output. Statin treatment activates autophagic flux in HepG2 cells. Acute suppression of autophagy with lysosome inhibitors in statin treated HepG2 cells reduced gluconeogenic enzymes expression and glucose output. Importantly, the ability of Statins to increase gluconeogenesis was impaired when ATG7 was deficient and BECN1 was absent, suggesting that autophagy plays a critical role in the diabetogenic effects of Statins. Moreover autophagic vacuoles and gluconeogenic genes expression in the liver of diet-induced obese mice were increased by Statins, ultimately leading to elevated hepatic glucose production, hyperglycemia, and insulin resistance. Together, these data demonstrate that chronic statin therapy results in insulin resistance through the activation of hepatic gluconeogenesis, which is tightly coupled to hepatic autophagy. These data further contribute to a better understanding of the diabetogenic effects of stains in the context of insulin resistance.
Aliya Sarmanova - One of the best experts on this subject based on the ideXlab platform.
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statin use and risk of joint replacement due to osteoarthritis and rheumatoid arthritis a propensity score matched longitudinal cohort study
Rheumatology, 2020Co-Authors: Aliya Sarmanova, Michael Doherty, Changfu Kuo, Jie Wei, Abhishek Abhishek, Christian D Mallen, Chao ZengAbstract:Objective Statins are reported to have a potential benefit on progression of OA and on disease activity in RA, but existing evidence is conflicting. Our objective was to examine whether Statins associate with reduction in the risk for joint replacement due to OA and RA. Methods This was a propensity score-matched cohort study. Electronic health records from the UK Clinical Practice Research Datalink were used. We selected people prescribed Statins and people never prescribed Statins. Each statin user was matched to a non-user by age, gender, practice and propensity score for statin prescription. The main outcome measures were knee or hip joint replacement overall, and specifically because of OA or RA. The association between Statins and risk of joint replacement was assessed using Cox proportional hazard regression. Statin exposure was categorized according to the potency of reducing low-density lipoprotein as low (21-28%), medium (32-38%) or high (42-55%) intensity. Results A total of 178 467 statin users were matched with 178 467 non-users by age, gender, practice and propensity score. Overall, statin was not associated with reduced risk of knee or hip replacement (hazard ratio 0.99, 95% CI: 0.97, 1.03), unless prescribed at high strength (0.86, 0.75-0.98). The reduced risk was only observed for joint replacement due to RA (0.77, 0.63-0.94) but not OA (0.97, 0.94-1.01). Conclusion Statins at high intensity may reduce the risk of hip or knee replacement. This effect may be RA specific. Further studies to investigate mechanisms of risk reduction and the impact in people with RA are warranted.
Kees G Hovingh - One of the best experts on this subject based on the ideXlab platform.
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statin therapy reduces plasma angiopoietin like 3 angptl3 concentrations in hypercholesterolemic patients via reduced liver x receptor lxr activation
Atherosclerosis, 2020Co-Authors: Laurens F Reeskamp, Kees G Hovingh, Tycho R Tromp, Roeland Huijgen, Erik S G Stroes, Aldo GrefhorstAbstract:Background and aims: Statins suppress hepatic mRNA expression of ANGPTL3 encoding angiopoietin-like 3 in healthy subjects, but it is unknown if plasma ANGPTL3 concentrations are affected by Statins prescribed to hypercholesterolemic patients in clinical practice. We therefore investigated the effect of statin treatment on plasma ANGPTL3 concentrations in hypercholesterolemic patients. In addition, we explored the underlying mechanism by which Statins regulate ANGPTL3 in vitro. Methods: Plasma ANGPTL3 concentrations were measured in 93 genetically confirmed familial hypercholesterolemia (FH) patients who were using statin therapy and 61 statin naive FH patients. Moreover, concentrations were measured in 14 hypercholesterolemic patients who discontinued their statin treatment for 4 weeks. In vitro studies were performed with Huh7 human hepatoma cells. Results: Plasma ANGPTL3 concentrations were 15% lower in statin treated FH patients compared to statin naive FH patients (145 (120-193) vs. 167 (135-220) ng/ml, p = 0.012). Statin discontinuation resulted in a 21% (p<0.001) increase of plasma ANGPTL3 concentrations. Simvastatin reduced ANGPTL3 mRNA expression and ANGPTL3 secretion of Huh7 cells. Liver X receptor (LXR) activation with T0901317 increased ANGPTL3 mRNA expression and ANGPTL3 secretion by 6- and 3-fold, respectively. Adding simvastatin did not mitigate this effect but adding the LXR antagonist GSK2230 to simvastatin-incubated Huh7 cells diminished simvastatin-induced reductions in ANGPTL3 mRNA expression and ANGPTL3 secretion. Simvastatin reduced intracellular oxysterol concentrations. Oxysterols are endogenous LXR ligands, implying that simvastatin suppresses ANGPTL3 secretion via reduced oxysterol-mediated LXR activation. Conclusions: Statins lower plasma ANGPTL3 concentrations in hypercholesterolemic patients, likely due to decreased oxysterol-mediated LXR activation.
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a systematic review and meta analysis of the effect of Statins on plasma asymmetric dimethylarginine concentrations
Scientific Reports, 2015Co-Authors: Corina Serban, Amirhossein Sahebkar, Sorin Ursoniu, Dimitri P Mikhailidis, Manfredi Rizzo, Kees G Hovingh, John J P Kastelein, Leszek Kalinowski, Jacek RyszAbstract:The impact of statin therapy on plasma asymmetric dimethylarginine (ADMA) levels has not been conclusively studied. Therefore the aim of the meta-analysis was to assess the effect of Statins on circulating ADMA levels. We searched selected databases (up to August 2014) to identify randomized controlled trials (RCTs) that investigate the effect of Statins on plasma ADMA concentrations. A weighted meta-regression (WMD) using unrestricted maximum likelihood model was performed to assess the impact of statin dose, duration of statin therapy and baseline ADMA concentrations as potential variables on the WMD between statin and placebo group. In total, 1134 participants in 9 selected RCTs were randomized; 568 were allocated to statin treatment and 566 were controls. There was a significant reduction in plasma ADMA concentrations following statin therapy compared with placebo (WMD: − 0.104 μM, 95% confidence interval: − 0.131 to − 0.077, Z = − 7.577, p < 0.0001). Subgroups analysis has shown a significant impact of hydrophilic Statins (WMD: − 0.207 μM, 95%CI: − 0.427 to + 0.013, Z = − 7.250, p < .0001) and a non-significant effect of hydrophobic Statins (WMD: − 0.101 μM, 95%CI: − 0.128 to − 0.074, Z = − 1.845, p = 0.065). In conclusion, this meta-analysis of available RCTs showed a significant reduction in plasma ADMA concentrations following therapy with hydrophilic Statins.
Obin Kwon - One of the best experts on this subject based on the ideXlab platform.
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Chronic HMGCR/HMG-CoA reductase inhibitor treatment contributes to dysglycemia by upregulating hepatic gluconeogenesis through autophagy induction
2018Co-Authors: Hye Jin Wang, Jae Yeo Park, Obin Kwon, Eun Yeong Choe, Chul Hoon Kim, Kyu Yeon Hur, Myung-shik Lee, Mijin Yun, Bong Soo Cha, Young-bum KimAbstract:Statins (HMGCR/HMG-CoA reductase [3-hydroxy-3-methylglutaryl-CoA reductase] inhibitors) are widely used to lower blood cholesterol levels but have been shown to increase the risk of type 2 diabetes mellitus. However, the molecular mechanism underlying diabetogenic effects remains to be elucidated. Here we show that Statins significantly increase the expression of key gluconeogenic enzymes (such as G6PC [glucose-6-phosphatase] and PCK1 (phosphoenolpyruvate carboxykinase 1 [soluble]) in vitro and in vivo and promote hepatic glucose output. Statin treatment activates autophagic flux in HepG2 cells. Acute suppression of autophagy with lysosome inhibitors in statin treated HepG2 cells reduced gluconeogenic enzymes expression and glucose output. Importantly, the ability of Statins to increase gluconeogenesis was impaired when ATG7 was deficient and BECN1 was absent, suggesting that autophagy plays a critical role in the diabetogenic effects of Statins. Moreover autophagic vacuoles and gluconeogenic genes expression in the liver of diet-induced obese mice were increased by Statins, ultimately leading to elevated hepatic glucose production, hyperglycemia, and insulin resistance. Together, these data demonstrate that chronic statin therapy results in insulin resistance through the activation of hepatic gluconeogenesis, which is tightly coupled to hepatic autophagy. These data further contribute to a better understanding of the diabetogenic effects of stains in the context of insulin resistance.
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chronic hmgcr hmg coa reductase inhibitor treatment contributes to dysglycemia by upregulating hepatic gluconeogenesis through autophagy induction
Autophagy, 2015Co-Authors: Hye Jin Wang, Jae Yeo Park, Obin Kwon, Eun Yeong Choe, Eun Seok KangAbstract:Statins (HMGCR/HMG-CoA reductase [3-hydroxy-3-methylglutaryl-CoA reductase] inhibitors) are widely used to lower blood cholesterol levels but have been shown to increase the risk of type 2 diabetes mellitus. However, the molecular mechanism underlying diabetogenic effects remains to be elucidated. Here we show that Statins significantly increase the expression of key gluconeogenic enzymes (such as G6PC [glucose-6-phosphatase] and PCK1 (phosphoenolpyruvate carboxykinase 1 [soluble]) in vitro and in vivo and promote hepatic glucose output. Statin treatment activates autophagic flux in HepG2 cells. Acute suppression of autophagy with lysosome inhibitors in statin treated HepG2 cells reduced gluconeogenic enzymes expression and glucose output. Importantly, the ability of Statins to increase gluconeogenesis was impaired when ATG7 was deficient and BECN1 was absent, suggesting that autophagy plays a critical role in the diabetogenic effects of Statins. Moreover autophagic vacuoles and gluconeogenic genes expression in the liver of diet-induced obese mice were increased by Statins, ultimately leading to elevated hepatic glucose production, hyperglycemia, and insulin resistance. Together, these data demonstrate that chronic statin therapy results in insulin resistance through the activation of hepatic gluconeogenesis, which is tightly coupled to hepatic autophagy. These data further contribute to a better understanding of the diabetogenic effects of stains in the context of insulin resistance.
