Is immunity a mechanism contributing to statin-induced diabetes?

Adipocyte

Volumn 4, Issue 4, 2015, Pages 232-238

  Henriksbo, Brandyn D ^a   Schertzer, Jonathan D ^a  

^a MCMASTER UNIVERSITY   (Canada)

Author keywords

Adipose; Cardiovascular disease; Cholesterol; Cytokine; IL 1; Inflammasome; Insulin resistance; Macrophage; NLRP3; Obesity

Indexed keywords

C REACTIVE PROTEIN; CHOLESTEROL; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; INFLAMMASOME; INTERLEUKIN 1BETA; INTERLEUKIN 1BETA CONVERTING ENZYME; INTERLEUKIN 6; PATTERN RECOGNITION RECEPTOR; STEROL REGULATORY ELEMENT BINDING PROTEIN; TUMOR NECROSIS FACTOR;

CARDIOVASCULAR RISK; DIABETES MELLITUS; DRUG INDUCED DISEASE; DYSGLYCEMIA; HUMAN; IMMUNITY; INFLAMMATION; INSULIN RESISTANCE; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; PLEIOTROPY; PROTEIN PRENYLATION; REVIEW; SINGLE NUCLEOTIDE POLYMORPHISM; STATIN INDUCED DIABETES;

EID: 84963761571     PISSN: 21623945     EISSN: 2162397X     Source Type: Journal    
DOI: 10.1080/21623945.2015.1024394     Document Type: Review

References (82)

1. Lindgren P, Jonsson B. Cost-effectiveness of statins revisited: lessons learned about the value of innovation. Eur J Health Econ 2012; 13:445-50. PMID:21528389. http://dx.doi.org/10.1007/s10198-011-0315-1
2. Jackevicius CA, Cox JL, Carreon D, Tu JV, Rinfret S, So D, Johansen H, Kalavrouziotis D, Demers V, Humphries K, et al. Long-term trends in use of and expenditures for cardiovascular medications in Canada. CMAJ 2009; 181:E19-28. PMID:19581604. http://dx.doi.org/10.1503/cmaj.081913
3. Hoeg JM, Brewer HB. 3-Hydroxy-3-methylglutaryl–coenzyme A reductase inhibitors in the treatment of hypercholesterolemia. JAMA 1987; 258:3532-6. PMID:3316727. http://dx.doi.org/10.1001/jama.1987.03400240064025
4. Bilheimer DW, Grundy SM, Brown MS, Goldstein JL. Mevinolin and colestipol stimulate receptor-mediated clearance of low density lipoprotein from plasma in familial hypercholesterolemia heterozygotes. Proc Natl Acad Sci U S A 1983; 80:4124-8. PMID:6575399. http://dx.doi.org/10.1073/pnas.80.13.4124
5. Greenwood J, Steinman L, Zamvil SS. Statin therapy and autoimmune disease: from protein prenylation to immunomodulation. Nat Rev Immunol 2006; 6:358-70. PMID:16639429. http://dx.doi.org/10.1038/nri1839
6. Waiczies S, Bendix I, Zipp F. Geranylgeranylation but not GTP-loading of Rho GTPases determines T cell function. Sci Signal 2008; 1:pt3. PMID:18364514. http://dx.doi.org/10.1126/stke.112pt3
7. Schonbeck U, Libby P. Inflammation, immunity, and HMG-CoA reductase inhibitors: statins as antiinflammatory agents? Circulation 2004; 109:II18-26. PMID:15173059
8. Blank N, Schiller M, Krienke S, Busse F, Schatz B, Ho AD, Kalden JR, Lorenz H-M. Atorvastatin Inhibits T cell activation through 3-hydroxy-3-methylglutaryl coenzyme a reductase without decreasing cholesterol synthesis. J Immunol 2007; 179:3613-21. PMID:17785796. http://dx.doi.org/10.4049/jimmunol.179.6.3613
9. Montecucco F, Mach F. Update on statin-mediated anti-inflammatory activities in atherosclerosis. Semin Immunopathol 2009; 31:127-42. PMID:19415282. http://dx.doi.org/10.1007/s00281-009-0150-y
10. Albert MA, Danielson E, Rifai N, Ridker PM. Effect of statin therapy on C-reactive protein levels. JAMA 2001; 286:64. PMID:11434828. http://dx.doi.org/10.1001/jama.286.1.64
11. Ridker PM, Cannon CP, Morrow D, Rifai N, Rose LM, McCabe CH, Pfeffer MA, Braunwald E. C-reactive protein levels and outcomes after statin therapy. N Engl J Med 2005; 352:20-8. PMID:15635109. http://dx.doi.org/10.1056/NEJMoa042378
12. Ridker PM. Moving beyond JUPITER: will inhibiting inflammation reduce vascular event rates? Curr Atheroscler Rep 2013; 15:295. PMID:23225175. http://dx.doi.org/10.1007/s11883-012-0295-3
13. Ando H, Takamura T, Ota T, Nagai Y, Kobayashi K. Cerivastatin improves survival of mice with lipopolysaccharide-induced sepsis. J Pharmacol Exp Ther 2000; 294:1043-6. PMID:10945857
14. Rosenson RS, Tangney CC, Casey LC. Inhibition of proinflammatory cytokine production by pravastatin. Lancet 1999; 353:983-4. PMID:10459915. http://dx.doi.org/10.1016/S0140-6736(98)05917-0
15. Kuijk LM, Mandey SH, Schellens I, Waterham HR, Rijkers GT, Coffer PJ, Frenkel J. Statin synergizes with LPS to induce IL-1beta release by THP-1 cells through activation of caspase-1. Mol Immunol 2008; 45:2158-65. PMID:18242710. http://dx.doi.org/10.1016/j.molimm.2007.12.008
16. Lindholm MW, Nilsson J. Simvastatin stimulates macrophage interleukin-1beta secretion through an isoprenylation-dependent mechanism. Vascul Pharmacol 2007; 46:91-6. PMID:16942919. http://dx.doi.org/10.1016/j.vph.2006.07.001
17. Mandey SHL, Kuijk LM, Frenkel J, Waterham HR. A role for geranylgeranylation in interleukin-1beta secretion. Arthritis Rheum 2006; 54:3690-5. PMID:17075828. http://dx.doi.org/10.1002/art.22194
18. Montero MT, Matilla J, Gomez-Mampaso E, Lasuncion MA. Geranylgeraniol regulates negatively caspase-1 autoprocessing: implication in the Th1 response against Mycobacterium tuberculosis. J Immunol 2004; 173:4936-44. PMID:15470035. http://dx.doi.org/10.4049/jimmunol.173.8.4936
19. Montero MT, Hernandez O, Suarez Y, Matilla J, Ferruelo AJ, Martınez-Botas J, Gomez-Coronado D, Lasuncion MA. Hydroxymethylglutaryl-coenzyme A reductase inhibition stimulates caspase-1 activity and Th1-cytokine release in peripheral blood mononuclear cells. Atherosclerosis 2000; 153:303-13. PMID:11164419. http://dx.doi.org/10.1016/S0021-9150(00)00417-2
20. Henriksbo BD, Lau TC, Cavallari JF, Denou E, Chi W, Lally JS, Crane JD, Duggan BM, Foley KP, Fullerton MD, et al. Fluvastatin causes NLRP3 inflammasome-mediated adipose insulin resistance. Diabetes 2014; 63:3742-7. PMID:24917577. http://dx.doi.org/10.2337/db13-1398
21. Sattar N, Preiss D, Murray HM, Welsh P, Buckley BM, de Craen AJM, Seshasai SRK, McMurray JJ, Freeman DJ, Jukema JW, et al. Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials. Lancet 2010; 375:735-42. PMID:20167359. http://dx.doi.org/10.1016/S0140-6736(09)61965-6
22. Ma T, Tien L, Fang C-L, Liou Y-S, Jong G-P. Statins and new-onset diabetes: a retrospective longitudinal cohort study. Clin Ther 2012;10:1-7.
23. Carter AA, Gomes T, Camacho X, Juurlink DN, Shah BR, Mamdani MM. Risk of incident diabetes among patients treated with statins: population based study. BMJ 2013; 346:f2610. PMID:23704171
24. Dormuth CR, Filion KB, Paterson JM, James MT, Teare GF, Raymond CB, Rahme E, Tamim H, Lipscombe L. Higher potency statins and the risk of new diabetes: multicentre, observational study of administrative databases. BMJ 2014; 348:g3244. PMID:24874977. http://dx.doi.org/10.1136/bmj.g3244
25. Cho Y, Choe E, Lee Y-H, Seo JW, Choi Y, Yun Y, Wang HJ, Ahn CW, Cha BS, Lee HC, et al. Risk of diabetes in patients treated with HMG-CoA reductase inhibitors. Metabolism 2014:1-7.
26. Freeman DJ, Norrie J, Sattar N, Neely RDG, Cobbe SM, Ford I, Isles C, Lorimer AR, Macfarlane PW, McKillop JH, et al. Pravastatin and the development of diabetes mellitus: rvidence for a protective treatment effect in the West of Scotland Coronary Prevention Study. Circulation 2001; 103:357-62. PMID:11157685. http://dx.doi.org/10.1161/01.CIR.103.3.357
27. Ridker PM, Danielson E, Fonseca FAH, Genest J, Gotto AM, Kastelein JJP, Koenig W, Libby P, Lorenzatti AJ, MacFadyen JG, et al. Rosuvastatin to prevent vascular events in men and women with elevated Creactive protein. N Engl J Med 2008; 359:2195-207. PMID:18997196. http://dx.doi.org/10.1056/NEJMoa0807646
28. Protection H, Collaborative S. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebocontrolled trial. Lancet 2002; 360:7-22. PMID:12114036. http://dx.doi.org/10.1016/S0140-6736(02)09327-3
29. Swerdlow DI, Sattar N. A dysglycaemic effect of statins in diabetes: relevance to clinical practice? Diabetologia 2014; 57:2433-5. PMID:25335441. http://dx.doi.org/10.1007/s00125-014-3409-3
30. Goldfine AB. Statins: is it really time to reassess benefits and risks? N Engl J Med 2012; 366:1752-5. PMID:22533536. http://dx.doi.org/10.1056/NEJMp1203020
31. Chatzizisis YS, Koskinas KC, Misirli G, Vaklavas C, Hatzitolios A, Giannoglou GD. Risk factors and drug interactions predisposing to statin-induced myopathy: implications for risk assessment, prevention and treatment. Drug Saf 2010; 33:171-87. PMID:20158283. http://dx.doi.org/10.2165/11319380-000000000-00000
32. Reiner _Z. Statins in the primary prevention of cardiovascular disease. Nat Rev Cardiol 2013; 10:453-64. PMID:23736519. http://dx.doi.org/10.1038/nrcardio.2013.80
33. Pencina MJ, Navar-Boggan AM, D’Agostino RB, Williams K, Neely B, Sniderman AD, Peterson ED. Application of new cholesterol guidelines to a populationbased sample. N Engl J Med 2014; 370:1422-31. PMID:24645848. http://dx.doi.org/10.1056/NEJMoa1315665
34. Seshasai SRK, Kaptoge S, Thompson A, Di Angelantonio E, Gao P, Sarwar N, Whincup PH, Mukamal KJ, Gillum RF, Holme I, et al. Diabetes mellitus, fasting glucose, and risk of cause-specific death. N Engl J Med 2011; 364:829-41. PMID:21366474. http://dx.doi.org/10.1056/NEJMoa1008862
35. Swerdlow DI, Preiss D, Kuchenbaecker KB, Holmes MV, Engmann JEL, Shah T, Sofat R, Stender S, Johnson PCD, Scott RA, et al. HMG-coenzyme A reductase inhibition, type 2 diabetes, and bodyweight: evidence from genetic analysis and randomised trials. Lancet 2014:1-11.
36. Fullerton MD, Steinberg GR, Schertzer JD. Immunometabolism of AMPK in insulin resistance and atherosclerosis. Mol Cell Endocrinol 2013; 366:224-34. PMID:22361321. http://dx.doi.org/10.1016/j.mce.2012.02.004
37. Schertzer JD, Steinberg GR. Immunometabolism: the interface of immune and metabolic responses in disease. Immunol Cell Biol 2014; 92:303. PMID:24613974. http://dx.doi.org/10.1038/icb.2014.12
38. Glass CK, Olefsky JM. Inflammation and lipid signaling in the etiology of insulin resistance. Cell Metab 2012; 15:635-45. PMID:22560216. http://dx.doi.org/10.1016/j.cmet.2012.04.001
39. Shi H, Kokoeva MV, Inouye K, Tzameli I, Yin H, Flier JS. TLR4 links innate immunity and fatty acid–induced insulin resistance. 2006; 116:3015-25. PMID:17053832
40. Konner AC, Bruning JC. Toll-like receptors: linking inflammation to metabolism. Trends Endocrinol Metab 2011; 22:16-23. PMID:20888253. http://dx.doi.org/10.1016/j.tem.2010.08.007
41. Chi W, Dao D, Lau TC, Henriksbo BD, Cavallari JF, Foley KP, Schertzer JD. Bacterial peptidoglycan stimulates adipocyte lipolysis via NOD1. PLoS One 2014; 9: e97675. PMID:24828250. http://dx.doi.org/10.1371/journal.pone.0097675
42. Schertzer JD, Tamrakar AK, Magalhaes JG, Pereira S, Bilan PJ, Fullerton MD, Liu Z, Steinberg GR, Giacca A, Philpott DJ, et al. NOD1 activators link innate immunity to insulin resistance. Diabetes 2011; 60:2206-15. PMID:21715553. http://dx.doi.org/10.2337/db11-0004
43. Tamrakar AK, Schertzer JD, Chiu TT, Foley KP, Bilan PJ, Philpott DJ, Klip A. NOD2 activation induces muscle cellautonomous innate immune responses and insulin resistance. Endocrinology 2010; 151:5624-37. PMID:20926588. http://dx.doi.org/10.1210/en.2010-0437
44. Zhou R, Tardivel A, Thorens B, Choi I, Tschopp J. Thioredoxin-interacting protein links oxidative stress to inflammasome activation. Nat Immunol 2010; 11:136-40. PMID:20023662. http://dx.doi.org/10.1038/ni.1831
45. Youm Y-H, Adijiang A, Vandanmagsar B, Burk D, Ravussin A, Dixit VD. Elimination of the NLRP3-ASC inflammasome protects against chronic obesityinduced pancreatic damage. Endocrinology 2011; 152:4039-45. PMID:21862613. http://dx.doi.org/10.1210/en.2011-1326
46. Lee H-M, Kim J-J, Kim HJ, Shong M, Ku BJ, Jo E-K. Upregulated NLRP3 inflammasome activation in patients with type 2 diabetes. Diabetes 2013; 62:194-204. PMID:23086037. http://dx.doi.org/10.2337/db12-0420
47. Vandanmagsar B, Youm Y-H, Ravussin A, Galgani JE, Stadler K, Mynatt RL, Ravussin E, Stephens JM, Dixit VD. The NLRP3 inflammasome instigates obesityinduced inflammation and insulin resistance. Nat Med 2011; 17:179-88. PMID:21217695. http://dx.doi.org/10.1038/nm.2279
48. Stienstra R, Joosten LAB, Koenen T, van Tits B, van Diepen JA, van den Berg SAA, Rensen PCN, Voshol PJ, Fantuzzi G, Hijmans A, et al. The inflammasomemediated caspase-1 activation controls adipocyte differentiation and insulin sensitivity. Cell Metab 2010; 12:593-605. PMID:21109192. http://dx.doi.org/10.1016/j.cmet.2010.11.011
49. Schroder K, Zhou R, Tschopp J. The NLRP3 inflammasome: a sensor for metabolic danger? Science 2010; 327:296-300. PMID:20075245. http://dx.doi.org/10.1126/science.1184003
50. Grant RW, Dixit VD. Mechanisms of disease: inflammasome activation and the development of type 2 diabetes. Front Immunol 2013; 4:50. PMID:23483669. http://dx.doi.org/10.3389/fimmu.2013.00050
51. Haneklaus M, O’Neill LA, Coll RC. Modulatory mechanisms controlling the NLRP3 inflammasome in inflammation: recent developments. Curr Opin Immunol 2013:2-7.
52. Bauernfeind FG, Horvath G, Stutz A, Alnemri ES, MacDonald K, Speert D, Fernandes-Alnemri T, Wu J, Monks BG, Fitzgerald KA, et al. Cutting edge: NFkappaB activating pattern recognition and cytokine receptors license NLRP3 inflammasome activation by regulating NLRP3 expression. J Immunol 2009; 183:787-91. PMID:19570822. http://dx.doi.org/10.4049/jimmunol.0901363
53. Kono H, Kimura Y, Latz E. Inflammasome activation in response to dead cells and their metabolites. Curr Opin Immunol 2014; 30:91-8. http://dx.doi.org/10.1016/j.coi.2014.09.001
54. Larsen CM, Faulenbach M, Vaag A, Vølund A, Ehses JA, Seifert B, Mandrup-Poulsen T, Donath MY. Interleukin-1-receptor antagonist in type 2 diabetes mellitus. N Engl J Med 2007; 356:1517-26. PMID:17429083. http://dx.doi.org/10.1056/NEJMoa065213
55. Ridker PM. Closing the loop on inflammation and atherothrombosis: why perform the CIRT and CANTOS trials? Trans Am Clin Climatol Assoc 2013; 124:174-90. PMID:23874021
56. Liao Y-H, Lin Y-C, Tsao S-T, Lin Y-C, Yang A-J, Huang C-T, Huang K-C, Lin WW. HMG-CoA reductase inhibitors activate caspase-1 in human monocytes depending on ATP release and P2_7 activation. J Leukoc Biol 2012; 92:1-11. PMID:22745457. http://dx.doi.org/10.1189/jlb.0312130
57. Lamkanfi M, Mueller JL, Vitari AC, Misaghi S, Fedorova A, Deshayes K, Lee WP, Hoffman HM, Dixit VM. Glyburide inhibits the Cryopyrin/Nalp3 inflammasome. J Cell Biol 2009; 187:61-70. PMID:19805629. http://dx.doi.org/10.1083/jcb.200903124
58. Jager J, Gremeaux T, Cormont M, Le Marchand-Brustel Y, Tanti J-F. Interleukin-1beta-induced insulin resistance in adipocytes through down-regulation of insulin receptor substrate-1 expression. Endocrinology 2007; 148:241-51. PMID:17038556. http://dx.doi.org/10.1210/en.2006-0692
59. Davaro F, Forde SD, Garfield M, Jiang Z, Halmen K, Tamburro ND, Kurt-Jones E, Fitzgerald KA, Golenbock DT, Wang D. 3-Hydroxyl-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor (Statin)-induced 28-kDa interleukin-1b interferes with mature IL-1b signaling. J Biol Chem 2014; 289:16214-22. PMID:24790079. http://dx.doi.org/10.1074/jbc.M114.571505
60. Bruun JM, Stallknecht B, Helge JW, Richelsen B. Interleukin-18 in plasma and adipose tissue: effects of obesity, insulin resistance, and weight loss. Eur J Endocrinol 2007; 157:465-71. PMID:17893261. http://dx.doi.org/10.1530/EJE-07-0206
61. Lindegaard B, Matthews VB, Brandt C, Hojman P, Allen TL, Estevez E, Watt MJ, Bruce CR, Mortensen OH, Syberg S, et al. Interleukin-18 activates skeletal muscle AMPK and reduces weight gain and insulin resistance in mice. Diabetes 2013; 62:3064-74. PMID:23670974. http://dx.doi.org/10.2337/db12-1095
62. Lamkanfi M, Kanneganti T-D, Van Damme P, Vanden Berghe T, Vanoverberghe I, Vandekerckhove J, Vandenabeele P, Gevaert K, Nunez G. Targeted peptidecentric proteomics reveals caspase-7 as a substrate of the caspase-1 inflammasomes. Mol Cell Proteomics 2008; 7:2350-63. PMID:18667412. http://dx.doi.org/10.1074/mcp.M800132-MCP200
63. Kahns S, Kalai M, Jakobsen LD, Clark BFC, Vandenabeele P, Jensen PH. Caspase-1 and caspase-8 cleave and inactivate cellular parkin. J Biol Chem 2003; 278:23376-80. PMID:12692130. http://dx.doi.org/10.1074/jbc.M300495200
64. Shao W, Yeretssian G, Doiron K, Hussain SN, Saleh M. The caspase-1 digestome identifies the glycolysis pathway as a target during infection and septic shock. J Biol Chem 2007; 282:36321-9. PMID:17959595. http://dx.doi.org/10.1074/jbc.M708182200
65. 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. PMID:25106875
66. Teresi RE, Planchon SM, Waite KA, Eng C. Regulation of the PTEN promoter by statins and SREBP. Hum Mol Genet 2008; 17:919-28. PMID:18065496. http://dx.doi.org/10.1093/hmg/ddm364
67. Taniguchi CM, Emanuelli B, Kahn CR. Critical nodes in signalling pathways: insights into insulin action. Nat Rev Mol Cell Biol 2006; 7:85-96. PMID:16493415. http://dx.doi.org/10.1038/nrm1837
68. Wagner BK, Kitami T, Gilbert TJ, Peck D, Ramanathan A, Schreiber SL, Golub TR, Mootha VK. Largescale chemical dissection of mitochondrial function. Nat Biotechnol 2008; 26:343-51. PMID:18297058. http://dx.doi.org/10.1038/nbt1387
69. Wagner BK, Gilbert TJ, Hanai J, Imamura S, Bodycombe NE, Bon RS, Waldmann H, Clemons PA, Sukhatme VP, Mootha VK. A small-molecule screening strategy to identify suppressors of statin myopathy. ACS Chem Biol 2011; 6:900-4. PMID:21732624. http://dx.doi.org/10.1021/cb200206w
70. Kaufmann P, Torok M, Zahno A, Waldhauser KM, Brecht K, Krahenbuhl S. Toxicity of statins on rat skeletal muscle mitochondria. Cell Mol Life Sci 2006; 63:2415-25. PMID:17013560. http://dx.doi.org/10.1007/s00018-006-6235-z
71. Thuc LC, Teshima Y, Takahashi N, Nagano-Torigoe Y, Ezaki K, Yufu K, Nakagawa M, Hara M, Saikawa T. Mitochondrial K(ATP) channels-derived reactive oxygen species activate pro-survival pathway in pravastatininduced cardioprotection. Apoptosis 2010; 15:669-78. PMID:20151195. http://dx.doi.org/10.1007/s10495-010-0473-0
72. Sanchez CA, Rodrıguez E, Varela E, Zapata E, Paez A, Masso FA, Montano LF, Loopez-Marure R. Statininduced inhibition of MCF-7 breast cancer cell proliferation is related to cell cycle arrest and apoptotic and necrotic cell death mediated by an enhanced oxidative stress. Cancer Invest 2008; 26:698-707. http://dx.doi.org/10.1080/07357900701874658
73. Munoz-Planillo R, Kuffa P, Martınez-Colon G, Smith BL, Rajendiran TM, Nunez G. K Cefflux is the common trigger of NLRP3 inflammasome activation by bacterial toxins and particulate matter. Immunity 2013; 38:1142-53. http://dx.doi.org/10.1016/j.immuni.2013.05.016
74. Sinensky M. Recent advances in the study of prenylated proteins. Biochim Biophys Acta–Mol Cell Biol Lipids 2000; 1484:93-106. http://dx.doi.org/10.1016/S1388-1981(00)00009-3
75. Stenmark H, Olkkonen VM. Protein family review The Rab GTPase family. 2001:1-7.
76. Spindler SR, Li R, Dhahbi JM, Yamakawa A, Mote P, Bodmer R, Ocorr K, Williams RT, Wang Y, Ablao KP. Statin treatment increases lifespan and improves cardiac health in Drosophila by decreasing specific protein prenylation. PLoS One 2012; 7:e39581. PMID:22737247. http://dx.doi.org/10.1371/journal.pone.0039581
77. Cani PD, Bibiloni R, Knauf C, Waget A, Neyrinck AM, Delzenne NM, Burcelin R. Changes in gut microbiota control metabolic endotoxemia-induced Inflammation in high-fat diet-induced obesity and diabetes in mice. Diabetes 2008; 57:1470-81. PMID:18305141. http://dx.doi.org/10.2337/db07-1403
78. Cani PD, Amar J, Iglesias MA, Poggi M, Knauf C, Bastelica D, Neyrinck AM, Fava F, Tuohy KM, Chabo C, et al. Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes 2007; 56:1761-72. PMID:17456850. http://dx.doi.org/10.2337/db06-1491
79. Steinberg GR, Schertzer JD. AMPK promotes macrophage fatty acid oxidative metabolism to mitigate inflammation: implications for diabetes and cardiovascular disease. Immunol Cell Biol 2014; 92:340-5. PMID:24638063. http://dx.doi.org/10.1038/icb.2014.11
80. Jourdan T, Godlewski G, Cinar R, Bertola A, Szanda G, Liu J, Tam J, Han T, Mukhopadhyay B, Skarulis MC, et al. Activation of the Nlrp3 inflammasome in infiltrating macrophages by endocannabinoids mediates beta cell loss in type 2 diabetes. Nat Med 2013; 19:1132-40. PMID:23955712. http://dx.doi.org/10.1038/nm.3265
81. Masters SL, Dunne A, Subramanian SL, Hull RL, Tannahill GM, Sharp FA, Becker C, Franchi L, Yoshihara E, Chen Z, et al. Activation of the NLRP3 inflammasome by islet amyloid polypeptide provides a mechanism for enhanced IL-1b in type 2 diabetes. Nat Immunol 2010; 11:897-904. PMID:20835230. http://dx.doi.org/10.1038/ni.1935
82. Mitchell P, Marette A. Statin-induced insulin resistance through inflammasome activation: sailing between scylla and charybdis. Diabetes 2014; 63:3569-71. PMID:25342725. http://dx.doi.org/10.2337/db14-1059