Minder CM, Blumenthal RS, Blaha MJ. Statins for primary prevention of cardiovascular disease: the benefits outweigh the risks. Curr Opin Cardiol. 2013;28(5):554–60.
Article
PubMed
Google Scholar
Baigent C, Blackwell L, Emberson J, Holland LE, Reith C, Bhala N, Peto R, Barnes EH, Keech A, Simes J, et al. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet. 2010;376(9753):1670–81.
Article
CAS
PubMed
Google Scholar
Endo A. The discovery and development of HMG-CoA reductase inhibitors. J Lipid Res. 1992;33(11):1569–82.
CAS
PubMed
Google Scholar
Liao JK, Laufs U. Pleiotropic effects of statins. Annu Rev Pharmacol Toxicol. 2005;45:89–118.
Article
CAS
PubMed
PubMed Central
Google Scholar
Lotta LA, Sharp SJ, Burgess S, Perry JRB, Stewart ID, Willems SM, Luan J, Ardanaz E, Arriola L, Balkau B, et al. Association between low-density lipoprotein cholesterol-lowering genetic variants and risk of type 2 diabetes: a meta-analysis. JAMA. 2016;316(13):1383–91.
Article
CAS
PubMed
PubMed Central
Google Scholar
Thakker D, Nair S, Pagada A, Jamdade V, Malik A. Statin use and the risk of developing diabetes: a network meta-analysis. Pharmacoepidemiol Drug Saf. 2016;25(10):1131–49.
Article
CAS
PubMed
Google Scholar
Betteridge DJ, Carmena R. The diabetogenic action of statins—mechanisms and clinical implications. Nat Rev Endocrinol. 2016;12(2):99–110.
Article
CAS
PubMed
Google Scholar
Lorza-Gil E, Salerno AG, Wanschel AC, Vettorazzi JF, Ferreira MS, Rentz T, Catharino RR, Oliveira HC. Chronic use of pravastatin reduces insulin exocytosis and increases beta-cell death in hypercholesterolemic mice. Toxicology. 2016;344–346:42–52.
Article
PubMed
Google Scholar
Lorza-Gil E, de Souza JC, Garcia-Arevalo M, Vettorazzi JF, Marques AC, Salerno AG, Trigo JR, Oliveira HCF. Coenzyme Q10 protects against beta-cell toxicity induced by pravastatin treatment of hypercholesterolemia. J Cell Physiol. 2019;234(7):11047–59. https://doi.org/10.1002/jcp.27932
Article
CAS
PubMed
Google Scholar
Koh KK, Quon MJ, Han SH, Lee Y, Kim SJ, Park JB, Shin EK. Differential metabolic effects of pravastatin and simvastatin in hypercholesterolemic patients. Atherosclerosis. 2009;204(2):483–90.
Article
CAS
PubMed
Google Scholar
Muscogiuri G, Sarno G, Gastaldelli A, Savastano S, Ascione A, Colao A, Orio F. The good and bad effects of statins on insulin sensitivity and secretion. Endocr Res. 2014;39(4):137–43.
Article
CAS
PubMed
Google Scholar
Baker WL, Talati R, White CM, Coleman CI. Differing effect of statins on insulin sensitivity in non-diabetics: a systematic review and meta-analysis. Diabetes Res Clin Pract. 2010;87(1):98–107.
Article
CAS
PubMed
Google Scholar
Nakata M, Nagasaka S, Kusaka I, Matsuoka H, Ishibashi S, Yada T. Effects of statins on the adipocyte maturation and expression of glucose transporter 4 (SLC2A4): implications in glycaemic control. Diabetologia. 2006;49(8):1881–92.
Article
CAS
PubMed
Google Scholar
Ogura T, Tanaka Y, Nakata T, Namikawa T, Kataoka H, Ohtsubo Y. Simvastatin reduces insulin-like growth factor-1 signaling in differentiating C2C12 mouse myoblast cells in an HMG-CoA reductase inhibition-independent manner. J Toxicol Sci. 2007;32(1):57–67.
Article
CAS
PubMed
Google Scholar
Kain V, Kapadia B, Misra P, Saxena U. Simvastatin may induce insulin resistance through a novel fatty acid mediated cholesterol independent mechanism. Sci Rep. 2015;5:13823.
Article
PubMed
PubMed Central
Google Scholar
Yaluri N, Modi S, Kokkola T. Simvastatin induces insulin resistance in L6 skeletal muscle myotubes by suppressing insulin signaling, GLUT4 expression and GSK-3β phosphorylation. Biochem Biophys Res Commun. 2016;480(2):194–200.
Article
CAS
PubMed
Google Scholar
Bonifacio A, Sanvee GM, Bouitbir J, Krähenbühl S. The AKT/mTOR signaling pathway plays a key role in statin-induced myotoxicity. Biochim Biophys Acta. 2015;1853(8):1841–9.
Article
CAS
PubMed
Google Scholar
Sanvee GM, Panajatovic MV, Bouitbir J, Krähenbühl S. Mechanisms of insulin resistance by simvastatin in C2C12 myotubes and in mouse skeletal muscle. Biochem Pharmacol. 2019;164:23–33.
Article
CAS
PubMed
Google Scholar
Tomlinson SS, Mangione KK. Potential adverse effects of statins on muscle. Phys Ther. 2005;85(5):459–65.
PubMed
Google Scholar
Velho JA, Okanobo H, Degasperi GR, Matsumoto MY, Alberici LC, Cosso RG, Oliveira HC, Vercesi AE. Statins induce calcium-dependent mitochondrial permeability transition. Toxicology. 2006;219(1–3):124–32.
Article
CAS
PubMed
Google Scholar
Kwak HB, Thalacker-Mercer A, Anderson EJ, Lin CT, Kane DA, Lee NS, Cortright RN, Bamman MM, Neufer PD. Simvastatin impairs ADP-stimulated respiration and increases mitochondrial oxidative stress in primary human skeletal myotubes. Free Radic Biol Med. 2012;52(1):198–207.
Article
CAS
PubMed
Google Scholar
La Guardia PG, Alberici LC, Ravagnani FG, Catharino RR, Vercesi AE. Protection of rat skeletal muscle fibers by either L-carnitine or coenzyme Q10 against statins toxicity mediated by mitochondrial reactive oxygen generation. Front Physiol. 2013;4:103.
Article
PubMed
PubMed Central
Google Scholar
Hanai J, Cao P, Tanksale P, Imamura S, Koshimizu E, Zhao J, Kishi S, Yamashita M, Phillips PS, Sukhatme VP, et al. The muscle-specific ubiquitin ligase atrogin-1/MAFbx mediates statin-induced muscle toxicity. J Clin Invest. 2007;117(12):3940–51.
CAS
PubMed
PubMed Central
Google Scholar
Tuckow AP, Jefferson SJ, Kimball SR, Jefferson LS. Simvastatin represses protein synthesis in the muscle-derived C2C12 cell line with a concomitant reduction in eukaryotic initiation factor 2B expression. Am J Physiol Endocrinol Metab. 2011;300(3):E564–70.
Article
CAS
PubMed
PubMed Central
Google Scholar
Larsen S, Vigelsø A, Dandanell S, Prats C, Dela F, Helge JW. Simvastatin-induced insulin resistance may be linked to decreased lipid uptake and lipid synthesis in human skeletal muscle: the LIFESTAT study. J Diabetes Res. 2018;2018:9257874.
Article
PubMed
PubMed Central
Google Scholar
Rebalka IA, Raleigh MJ, Snook LA, Rebalka AN, MacPherson RE, Wright DC, Schertzer JD, Hawke TJ. Statin therapy alters lipid storage in diabetic skeletal muscle. Front Endocrinol (Lausanne). 2016;7:95.
Article
PubMed Central
Google Scholar
Bassel-Duby R, Olson EN. Signaling pathways in skeletal muscle remodeling. Annu Rev Biochem. 2006;75:19–37.
Article
CAS
PubMed
Google Scholar
Wang X, Hu Z, Hu J, Du J, Mitch WE. Insulin resistance accelerates muscle protein degradation: activation of the ubiquitin-proteasome pathway by defects in muscle cell signaling. Endocrinology. 2006;147(9):4160–8.
Article
CAS
PubMed
Google Scholar
Mitch WE, Goldberg AL. Mechanisms of muscle wasting. The role of the ubiquitin-proteasome pathway. N Engl J Med. 1996;335(25):1897–905.
Article
CAS
PubMed
Google Scholar
Kobayashi M, Chisaki I, Narumi K, Hidaka K, Kagawa T, Itagaki S, Hirano T, Iseki K. Association between risk of myopathy and cholesterol-lowering effect: a comparison of all statins. Life Sci. 2008;82(17–18):969–75.
Article
CAS
PubMed
Google Scholar
Johnson J, Carson K, Williams H, Karanam S, Newby A, Angelini G, George S, Jackson C. Plaque rupture after short periods of fat feeding in the apolipoprotein E-knockout mouse: model characterization and effects of pravastatin treatment. Circulation. 2005;111(11):1422–30.
Article
CAS
PubMed
Google Scholar
Liu SL, Li YH, Shi GY, Jiang MJ, Chang JH, Wu HL. The effect of statin on the aortic gene expression profiling. Int J Cardiol. 2007;114(1):71–7.
Article
PubMed
Google Scholar
Bisgaier CL, Essenburg AD, Auerbach BJ, Pape ME, Sekerke CS, Gee A, Wölle S, Newton RS. Attenuation of plasma low density lipoprotein cholesterol by select 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors in mice devoid of low density lipoprotein receptors. J Lipid Res. 1997;38(12):2502–15.
CAS
PubMed
Google Scholar
Cruz B, Gomes-Marcondes MC. Leucine-rich diet supplementation modulates foetal muscle protein metabolism impaired by Walker-256 tumour. Reprod Biol Endocrinol. 2014;12:2.
Article
PubMed
PubMed Central
Google Scholar
Taha DA, De Moor CH, Barrett DA, Lee JB, Gandhi RD, Hoo CW, Gershkovich P. The role of acid-base imbalance in statin-induced myotoxicity. Transl Res. 2016;174(140–160):e114.
Google Scholar
Sun B, Zhong Z, Wang F, Xu J, Xu F, Kong W, Ling Z, Shu N, Li Y, Wu T, et al. Atorvastatin impaired glucose metabolism in C2C12 cells partly via inhibiting cholesterol-dependent glucose transporter 4 translocation. Biochem Pharmacol. 2018;150:108–19.
Article
CAS
PubMed
Google Scholar
Mullen PJ, Lüscher B, Scharnagl H, Krähenbühl S, Brecht K. Effect of simvastatin on cholesterol metabolism in C2C12 myotubes and HepG2 cells, and consequences for statin-induced myopathy. Biochem Pharmacol. 2010;79(8):1200–9.
Article
CAS
PubMed
Google Scholar
Schirris TJ, Renkema GH, Ritschel T, Voermans NC, Bilos A, van Engelen BG, Brandt U, Koopman WJ, Beyrath JD, Rodenburg RJ, et al. Statin-induced myopathy is associated with mitochondrial complex III inhibition. Cell Metab. 2015;22(3):399–407.
Article
CAS
PubMed
Google Scholar
Sattar N, Preiss D, Murray HM, Welsh P, Buckley BM, de Craen AJ, Seshasai SR, McMurray JJ, Freeman DJ, Jukema JW, et al. Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials. Lancet. 2010;375(9716):735–42.
Article
CAS
PubMed
Google Scholar
Preiss D, Seshasai SR, Welsh P, Murphy SA, Ho JE, Waters DD, DeMicco DA, Barter P, Cannon CP, Sabatine MS, et al. Risk of incident diabetes with intensive-dose compared with moderate-dose statin therapy: a meta-analysis. JAMA. 2011;305(24):2556–64.
Article
CAS
PubMed
Google Scholar
Dormuth CR, Filion KB, Paterson JM, James MT, Teare GF, Raymond CB, Rahme E, Tamim H, Lipscombe L. Investigators CNfODES: higher potency statins and the risk of new diabetes: multicentre, observational study of administrative databases. BMJ. 2014;348:g3244.
Article
PubMed
PubMed Central
Google Scholar
Cederberg H, Stančáková A, Yaluri N, Modi S, Kuusisto J, Laakso M. Increased risk of diabetes with statin treatment is associated with impaired insulin sensitivity and insulin secretion: a 6 year follow-up study of the METSIM cohort. Diabetologia. 2015;58(5):1109–17.
Article
CAS
PubMed
Google Scholar
Cai R, Yuan Y, Sun J, Xia W, Huang R, Tian S, Dong X, Shen Y, Wang S. Statins worsen glycemic control of T2DM in target LDL-c level and LDL-c reduction dependent manners: a meta-analysis. Expert Opin Pharmacother. 2016;17(14):1839–49.
Article
CAS
PubMed
Google Scholar
Sasaki J, Iwashita M, Kono S. Statins: beneficial or adverse for glucose metabolism. J Atheroscler Thromb. 2006;13(3):123–9.
Article
CAS
PubMed
Google Scholar
Shepherd J, Blauw GJ, Murphy MB, Bollen EL, Buckley BM, Cobbe SM, Ford I, Gaw A, Hyland M, Jukema JW, et al. Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet. 2002;360(9346):1623–30.
Article
CAS
PubMed
Google Scholar
Busanello ENB, Marques AC, Lander N, de Oliveira DN, Catharino RR, Oliveira HCF, Vercesi AE. Pravastatin chronic treatment sensitizes hypercholesterolemic mice muscle to mitochondrial permeability transition: protection by creatine or coenzyme Q. Front Pharmacol. 2017;8:185.
Article
PubMed
PubMed Central
Google Scholar
Marques AC, Busanello ENB, de Oliveira DN, Catharino RR, Oliveira HCF, Vercesi AE. Coenzyme Q10 or creatine counteract pravastatin-induced liver redox changes in hypercholesterolemic mice. Front Pharmacol. 2018;9:685.
Article
PubMed
PubMed Central
Google Scholar
Graham DJ, Staffa JA, Shatin D, Andrade SE, Schech SD, La Grenade L, Gurwitz JH, Chan KA, Goodman MJ, Platt R. Incidence of hospitalized rhabdomyolysis in patients treated with lipid-lowering drugs. JAMA. 2004;292(21):2585–90.
Article
CAS
PubMed
Google Scholar
Pedro-Botet J, Millán Núñez-Cortés J, Chillarón JJ, Flores-Le Roux JA, Rius J. Severity of statin-induced adverse effects on muscle and associated conditions: data from the DAMA study. Expert Opin Drug Saf. 2016;15(12):1583–7.
Article
CAS
PubMed
Google Scholar
Thompson PD, Clarkson P, Karas RH. Statin-associated myopathy. JAMA. 2003;289(13):1681–90.
Article
CAS
PubMed
Google Scholar
Dirks AJ, Jones KM. Statin-induced apoptosis and skeletal myopathy. Am J Physiol Cell Physiol. 2006;291(6):C1208–12.
Article
CAS
PubMed
Google Scholar
Argilés JM, López-Soriano FJ, Busquets S. Apoptosis signalling is essential and precedes protein degradation in wasting skeletal muscle during catabolic conditions. Int J Biochem Cell Biol. 2008;40(9):1674–8.
Article
PubMed
Google Scholar
Bouitbir J, Charles AL, Echaniz-Laguna A, Kindo M, Daussin F, Auwerx J, Piquard F, Geny B, Zoll J. Opposite effects of statins on mitochondria of cardiac and skeletal muscles: a ‘mitohormesis’ mechanism involving reactive oxygen species and PGC-1. Eur Heart J. 2012;33(11):1397–407.
Article
CAS
PubMed
Google Scholar
Venero CV, Thompson PD. Managing statin myopathy. Endocrinol Metab Clin North Am. 2009;38(1):121–36.
Article
CAS
PubMed
Google Scholar
Urso ML, Clarkson PM, Hittel D, Hoffman EP, Thompson PD. Changes in ubiquitin proteasome pathway gene expression in skeletal muscle with exercise and statins. Arterioscler Thromb Vasc Biol. 2005;25(12):2560–6.
Article
CAS
PubMed
Google Scholar
Datta SR, Dudek H, Tao X, Masters S, Fu H, Gotoh Y, Greenberg ME. Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery. Cell. 1997;91(2):231–41.
Article
CAS
PubMed
Google Scholar
Gottlob K, Majewski N, Kennedy S, Kandel E, Robey RB, Hay N. Inhibition of early apoptotic events by Akt/PKB is dependent on the first committed step of glycolysis and mitochondrial hexokinase. Genes Dev. 2001;15(11):1406–18.
Article
CAS
PubMed
PubMed Central
Google Scholar
Schiaffino S, Mammucari C. Regulation of skeletal muscle growth by the IGF1-Akt/PKB pathway: insights from genetic models. Skelet Muscle. 2011;1(1):4.
Article
CAS
PubMed
PubMed Central
Google Scholar
Andres AM, Hernandez G, Lee P, Huang C, Ratliff EP, Sin J, Thornton CA, Damasco MV, Gottlieb RA. Mitophagy is required for acute cardioprotection by simvastatin. Antioxid Redox Signal. 2014;21(14):1960–73.
Article
CAS
PubMed
PubMed Central
Google Scholar
Souto Padron de Figueiredo A, Salmon AB, Bruno F, Jimenez F, Martinez HG, Halade GV, Ahuja SS, Clark RA, DeFronzo RA, Abboud HE, et al. Nox2 mediates skeletal muscle insulin resistance induced by a high fat diet. J Biol Chem. 2015;290(21):13427–39.
Article
PubMed
PubMed Central
Google Scholar
Sandri M, Sandri C, Gilbert A, Skurk C, Calabria E, Picard A, Walsh K, Schiaffino S, Lecker SH, Goldberg AL. Foxo transcription factors induce the atrophy-related ubiquitin ligase atrogin-1 and cause skeletal muscle atrophy. Cell. 2004;117(3):399–412.
Article
CAS
PubMed
PubMed Central
Google Scholar
Birnbaum Y, Nanhwan MK, Ling S, Perez-Polo JR, Ye Y, Bajaj M. PTEN upregulation may explain the development of insulin resistance and type 2 diabetes with high dose statins. Cardiovasc Drugs Ther. 2014;28(5):447–57.
Article
CAS
PubMed
Google Scholar
El-Ganainy SO, El-Mallah A, Abdallah D, Khattab MM, Mohy El-Din MM, El-Khatib AS. Elucidation of the mechanism of atorvastatin-induced myopathy in a rat model. Toxicology. 2016;359–360:29–38.
Article
PubMed
Google Scholar