{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T00:14:35Z","timestamp":1791850475184,"version":"4.3.4"},"reference-count":122,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2019,12,9]],"date-time":"2019-12-09T00:00:00Z","timestamp":1575849600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>The inflammasome is a multiprotein complex that acts to enhance inflammatory responses by promoting the production and secretion of key cytokines. The best-known inflammasome is the NLRP3 (nucleotide-binding oligomerization domain-like receptor [NLR] family pyrin domain-containing 3) inflammasome. The evidence has shown that the NLRP3 inflammasome, IL-1\u03b2, thioredoxin-interacting protein (TXNIP), and pyroptosis play vital roles in the development of diabetes. This review summarizes the regulation of type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) by NLRP3 via modulation of glucose tolerance, insulin resistance, inflammation, and apoptosis mediated by endoplasmic reticulum stress in adipose tissue. Moreover, NLRP3 participates in intestinal homeostasis and inflammatory conditions, and NLRP3-deficient mice experience intestinal lesions. The diversity of an individual\u2019s gut microbiome and the resultant microbial metabolites determines the extent of their involvement in the physiological and pathological mechanisms within the gut. As such, further study of the interaction between the NLRP3 inflammasome and the complex intestinal environment in disease development is warranted to discover novel therapies for the treatment of diabetes.<\/jats:p>","DOI":"10.3390\/biom9120850","type":"journal-article","created":{"date-parts":[[2019,12,9]],"date-time":"2019-12-09T11:22:51Z","timestamp":1575890571000},"page":"850","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":230,"title":["Modulatory Mechanisms of the NLRP3 Inflammasomes in Diabetes"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0017-680X","authenticated-orcid":false,"given":"Sujuan","family":"Ding","sequence":"first","affiliation":[{"name":"College of Bioscience and Biotechnology, Hunan Agricultural University, Changsha 410128, Hunan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng","family":"Xu","sequence":"additional","affiliation":[{"name":"College of Life Sciences, Shandong Agricultural University, Tai\u2019an 271018, Shandong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Ma","sequence":"additional","affiliation":[{"name":"College of Bioscience and Biotechnology, Hunan Agricultural University, Changsha 410128, Hunan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9475-5134","authenticated-orcid":false,"given":"Gang","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Bioscience and Biotechnology, Hunan Agricultural University, Changsha 410128, Hunan, China"},{"name":"Hunan Provincial Key Laboratory of Animal Nutritional Physiology and Metabolic Process, CAS Key Laboratory of Agro-ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, Chinese Academy of Sciences, National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Changsha 410125, Hunan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongmei","family":"Jang","sequence":"additional","affiliation":[{"name":"College of Bioscience and Biotechnology, Hunan Agricultural University, Changsha 410128, Hunan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Fang","sequence":"additional","affiliation":[{"name":"College of Bioscience and Biotechnology, Hunan Agricultural University, Changsha 410128, Hunan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,12,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.diabres.2018.02.023","article-title":"IDF Diabetes Atlas: Global estimates of diabetes prevalence for 2017 and projections for 2045","volume":"138","author":"Cho","year":"2018","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1160","DOI":"10.1016\/j.cell.2012.02.010","article-title":"Diabetes mellitus and the beta cell: The last ten years","volume":"148","author":"Ashcroft","year":"2012","journal-title":"Cell"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.diabres.2014.04.006","article-title":"Inflammation as a link between obesity, metabolic syndrome and type 2 diabetes","volume":"105","author":"Esser","year":"2014","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1038\/nri2925","article-title":"Type 2 diabetes as an inflammatory disease","volume":"11","author":"Donath","year":"2011","journal-title":"Nat. Rev. Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1007\/s00125-018-4760-6","article-title":"Neoepitopes: A new take on beta cell autoimmunity in type 1 diabetes","volume":"62","author":"Mannering","year":"2019","journal-title":"Diabetologia"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1111\/j.1464-5491.2007.02346.x","article-title":"Quality of life and treatment satisfaction in adults with Type 1 diabetes: A comparison between continuous subcutaneous insulin infusion and multiple daily injections","volume":"25","author":"Nicolucci","year":"2008","journal-title":"Diabet. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1083\/jcb.201602089","article-title":"The cell biology of inflammasomes: Mechanisms of inflammasome activation and regulation","volume":"213","author":"Sharma","year":"2016","journal-title":"J. Cell Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1186\/s12974-019-1498-0","article-title":"NLRP3 inflammasome as a potential treatment in ischemic stroke concomitant with diabetes","volume":"16","author":"Hong","year":"2019","journal-title":"J. Neuroinflamm."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2116","DOI":"10.1002\/jcp.25930","article-title":"NLRP3 inflammasome: Its regulation and involvement in atherosclerosis","volume":"233","author":"Hoseini","year":"2018","journal-title":"J. Cell. Physiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"787","DOI":"10.4049\/jimmunol.0901363","article-title":"Cutting edge: NF-kappaB activating pattern recognition and cytokine receptors license NLRP3 inflammasome activation by regulating NLRP3 expression","volume":"183","author":"Bauernfeind","year":"2009","journal-title":"J. Immunol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1038\/s41419-019-1413-8","article-title":"Recent advances in the mechanisms of NLRP3 inflammasome activation and its inhibitors","volume":"10","author":"Yang","year":"2019","journal-title":"Cell Death Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2324","DOI":"10.1182\/blood-2008-03-146720","article-title":"Differential requirement for the activation of the inflammasome for processing and release of IL-1beta in monocytes and macrophages","volume":"113","author":"Netea","year":"2009","journal-title":"Blood"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1016\/j.immuni.2016.01.012","article-title":"Human Monocytes Engage an Alternative Inflammasome Pathway","volume":"44","author":"Gaidt","year":"2016","journal-title":"Immunity"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2179","DOI":"10.1111\/dom.13350","article-title":"Peripheral cannabinoid 1 receptor blockade mitigates adipose tissue inflammation via NLRP3 inflammasome in mouse models of obesity","volume":"20","author":"Han","year":"2018","journal-title":"Diabetes Obes. Metab."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.metabol.2017.10.015","article-title":"Deactivation of the NLRP3 inflammasome in infiltrating macrophages by duodenal-jejunal bypass surgery mediates improvement of beta cell function in type 2 diabetes","volume":"81","author":"Wu","year":"2018","journal-title":"Metab. Clin. Exp."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"11318","DOI":"10.1073\/pnas.1513509112","article-title":"NLRP3 deficiency protects from type 1 diabetes through the regulation of chemotaxis into the pancreatic islets","volume":"112","author":"Hu","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1202","DOI":"10.1136\/annrheumdis-2013-203276","article-title":"Evidence of NLRP3-inflammasome activation in rheumatoid arthritis (RA); genetic variants within the NLRP3-inflammasome complex in relation to susceptibility to RA and response to anti-TNF treatment","volume":"73","author":"Mathews","year":"2014","journal-title":"Ann. Rheum. Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1038\/nature13322","article-title":"Negative regulation of the NLRP3 inflammasome by A20 protects against arthritis","volume":"512","author":"Walle","year":"2014","journal-title":"Nature"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1186\/s12974-018-1178-5","article-title":"PM2.5 exposure aggravates oligomeric amyloid beta-induced neuronal injury and promotes NLRP3 inflammasome activation in an in vitro model of Alzheimer\u2019s disease","volume":"15","author":"Wang","year":"2018","journal-title":"J. Neuroinflamm."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1038\/nrgastro.2015.94","article-title":"Inflammasome activation and function in liver disease","volume":"12","author":"Szabo","year":"2015","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"288","DOI":"10.3389\/fimmu.2012.00288","article-title":"NLRP3-Inflammasome Activating DAMPs Stimulate an Inflammatory Response in Glia in the Absence of Priming Which Contributes to Brain Inflammation after Injury","volume":"3","author":"Savage","year":"2012","journal-title":"Front. Immunol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1142","DOI":"10.1016\/j.immuni.2013.05.016","article-title":"K(+) efflux is the common trigger of NLRP3 inflammasome activation by bacterial toxins and particulate matter","volume":"38","author":"Kuffa","year":"2013","journal-title":"Immunity"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1038\/nm.3806","article-title":"A small-molecule inhibitor of the NLRP3 inflammasome for the treatment of inflammatory diseases","volume":"21","author":"Coll","year":"2015","journal-title":"Nat. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"4092","DOI":"10.1038\/s41467-018-06522-5","article-title":"Targeting of NLRP3 inflammasome with gene editing for the amelioration of inflammatory diseases","volume":"9","author":"Xu","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1038\/s41467-017-00227-x","article-title":"CLICs-dependent chloride efflux is an essential and proximal upstream event for NLRP3 inflammasome activation","volume":"8","author":"Tang","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"12504","DOI":"10.1038\/ncomms12504","article-title":"Fenamate NSAIDs inhibit the NLRP3 inflammasome and protect against Alzheimer\u2019s disease in rodent models","volume":"7","author":"Daniels","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1038\/cr.2011.20","article-title":"Mitochondrial ROS fuel the inflammasome","volume":"21","author":"Sorbara","year":"2011","journal-title":"Cell Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"4215","DOI":"10.1007\/s00018-012-1140-0","article-title":"NLRP3 inflammasome activation in macrophage cell lines by prion protein fibrils as the source of IL-1beta and neuronal toxicity","volume":"69","author":"Bencina","year":"2012","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1016\/j.bbi.2016.12.014","article-title":"Inhibiting the NLRP3 inflammasome with MCC950 promotes non-phlogistic clearance of amyloid-beta and cognitive function in APP\/PS1 mice","volume":"61","author":"Dempsey","year":"2017","journal-title":"Brain Behav. Immun."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1038\/nature15541","article-title":"Caspase-11 cleaves gasdermin D for non-canonical inflammasome signalling","volume":"526","author":"Kayagaki","year":"2015","journal-title":"Nature"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2918","DOI":"10.1002\/eji.201545655","article-title":"NLRP3 inflammasome activation downstream of cytoplasmic LPS recognition by both caspase-4 and caspase-5","volume":"45","author":"Baker","year":"2015","journal-title":"Eur. J. Immunol."},{"key":"ref_32","first-page":"270","article-title":"The mitochondrial Na(+)\/Ca(2+) exchanger may reduce high glucose-induced oxidative stress and nucleotide-binding oligomerization domain receptor 3 inflammasome activation in endothelial cells","volume":"12","author":"Zu","year":"2015","journal-title":"J. Geriatr. Cardiol. JGC"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"E825","DOI":"10.1152\/ajpendo.00296.2016","article-title":"Saturated fatty acids activate caspase-4\/5 in human monocytes, triggering IL-1beta and IL-18 release","volume":"311","author":"Pillon","year":"2016","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1146\/annurev-nutr-071816-064836","article-title":"Fatty Acids and NLRP3 Inflammasome-Mediated Inflammation in Metabolic Tissues","volume":"37","author":"Ralston","year":"2017","journal-title":"Annu. Rev. Nutr."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1126\/science.1241244","article-title":"The health risk of obesity--better metrics imperative","volume":"341","author":"Ahima","year":"2013","journal-title":"Science"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1038\/35007508","article-title":"Obesity as a medical problem","volume":"404","author":"Kopelman","year":"2000","journal-title":"Nature"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1016\/j.ijsu.2018.02.058","article-title":"Risk factor, early diagnosis and overall survival on outcome of association between pancreatic cancer and diabetes mellitus: Changes and advances, a review","volume":"52","author":"Khadka","year":"2018","journal-title":"Int. J. Surg."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1016\/j.gastro.2005.05.007","article-title":"Probability of pancreatic cancer following diabetes: A population-based study","volume":"129","author":"Chari","year":"2005","journal-title":"Gastroenterology"},{"key":"ref_39","unstructured":"World Health Organization (2016). Global Report on Diabetes, World Health Organization."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1250","DOI":"10.1038\/cr.2014.120","article-title":"Liver Med23 ablation improves glucose and lipid metabolism through modulating FOXO1 activity","volume":"24","author":"Chu","year":"2014","journal-title":"Cell Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"104","DOI":"10.2337\/db13-1747","article-title":"Pancreastatin-dependent inflammatory signaling mediates obesity-induced insulin resistance","volume":"64","author":"Bandyopadhyay","year":"2015","journal-title":"Diabetes"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"3160","DOI":"10.1016\/j.ijcard.2013.07.150","article-title":"An overview of the crosstalk between inflammatory processes and metabolic dysregulation during diabetic cardiomyopathy","volume":"168","author":"Palomer","year":"2013","journal-title":"Int. J. Cardiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1016\/j.molmet.2016.05.016","article-title":"Gut microbiota and immune crosstalk in metabolic disease","volume":"5","author":"Burcelin","year":"2016","journal-title":"Mol. Metab."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1111\/1574-6976.12075","article-title":"The first 1000 cultured species of the human gastrointestinal microbiota","volume":"38","year":"2014","journal-title":"FEMS Microbiol. Rev."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1038\/ni.2635","article-title":"Innate immune recognition of the microbiota promotes host-microbial symbiosis","volume":"14","author":"Chu","year":"2013","journal-title":"Nat. Immunol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1002\/jcb.22208","article-title":"Study of the proinflammatory role of human differentiated omental adipocytes","volume":"107","author":"Bassols","year":"2009","journal-title":"J. Cell. Biochem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1038\/nature12198","article-title":"Gut metagenome in European women with normal, impaired and diabetic glucose control","volume":"498","author":"Karlsson","year":"2013","journal-title":"Nature"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1126\/science.7678183","article-title":"Adipose expression of tumor necrosis factor-alpha: Direct role in obesity-linked insulin resistance","volume":"259","author":"Hotamisligil","year":"1993","journal-title":"Science"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"259","DOI":"10.15252\/emmm.201404169","article-title":"Defective NOD2 peptidoglycan sensing promotes diet-induced inflammation, dysbiosis, and insulin resistance","volume":"7","author":"Denou","year":"2015","journal-title":"EMBO Mol. Med."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1761","DOI":"10.2337\/db06-1491","article-title":"Metabolic endotoxemia initiates obesity and insulin resistance","volume":"56","author":"Cani","year":"2007","journal-title":"Diabetes"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1809","DOI":"10.2337\/dc10-2197","article-title":"Bacterial endotoxin activity in human serum is associated with dyslipidemia, insulin resistance, obesity, and chronic inflammation","volume":"34","author":"Lassenius","year":"2011","journal-title":"Diabetes Care"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1210\/er.2017-00192","article-title":"Evaluating Causality of Gut Microbiota in Obesity and Diabetes in Humans","volume":"39","author":"Meijnikman","year":"2018","journal-title":"Endocr. Rev."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Cao, M., Wang, P., Sun, C., He, W., and Wang, F. (2013). Amelioration of IFN-gamma and TNF-alpha-induced intestinal epithelial barrier dysfunction by berberine via suppression of MLCK-MLC phosphorylation signaling pathway. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0061944"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"American Diabetes Association (2013). Diagnosis and classification of diabetes mellitus. Diabetes Care, 36, S67\u2013S74.","DOI":"10.2337\/dc13-S067"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Atkinson, M.A. (2012). The pathogenesis and natural history of type 1 diabetes. Cold Spring Harb. Perspect. Med., 2.","DOI":"10.1101\/cshperspect.a007641"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2487","DOI":"10.1007\/s00125-013-3023-9","article-title":"Obesity phenotype is related to NLRP3 inflammasome activity and immunological profile of visceral adipose tissue","volume":"56","author":"Esser","year":"2013","journal-title":"Diabetologia"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1132","DOI":"10.1038\/nm.3265","article-title":"Activation of the Nlrp3 inflammasome in infiltrating macrophages by endocannabinoids mediates beta cell loss in type 2 diabetes","volume":"19","author":"Jourdan","year":"2013","journal-title":"Nat. Med."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1053\/j.gastro.2010.03.052","article-title":"Toll-like receptor 9 promotes steatohepatitis by induction of interleukin-1beta in mice","volume":"139","author":"Miura","year":"2010","journal-title":"Gastroenterology"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"4432","DOI":"10.4049\/jimmunol.0900576","article-title":"Monocytes from patients with type 1 diabetes spontaneously secrete proinflammatory cytokines inducing Th17 cells","volume":"183","author":"Bradshaw","year":"2009","journal-title":"J. Immunol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"59206","DOI":"10.1155\/MI\/2006\/59206","article-title":"Serum IL-1beta, IL-2, and IL-6 in insulin-dependent diabetic children","volume":"2006","author":"Dogan","year":"2006","journal-title":"Mediat. Inflamm."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1038\/icb.2017.23","article-title":"Negative regulators and their mechanisms in NLRP3 inflammasome activation and signaling","volume":"95","author":"Kim","year":"2017","journal-title":"Immunol. Cell Biol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1210\/jc.2007-2185","article-title":"Increased toll-like receptor (TLR) 2 and TLR4 expression in monocytes from patients with type 1 diabetes: Further evidence of a proinflammatory state","volume":"93","author":"Devaraj","year":"2008","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Netea, M.G., Simon, A., van de Veerdonk, F., Kullberg, B.J., Van der Meer, J.W., and Joosten, L.A. (2010). IL-1beta processing in host defense: Beyond the inflammasomes. PLoS Pathog., 6.","DOI":"10.1371\/journal.ppat.1000661"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/j.jbspin.2011.02.004","article-title":"Is caspase 1 central to activation of interleukin-1?","volume":"78","author":"Wittmann","year":"2011","journal-title":"Jt. Bone Spine Rev. Rhum."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1016\/j.immuni.2012.01.009","article-title":"Oxidized mitochondrial DNA activates the NLRP3 inflammasome during apoptosis","volume":"36","author":"Shimada","year":"2012","journal-title":"Immunity"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"164","DOI":"10.3389\/fimmu.2017.00164","article-title":"Mitochondrial DNA Activates the NLRP3 Inflammasome and Predisposes to Type 1 Diabetes in Murine Model","volume":"8","author":"Carlos","year":"2017","journal-title":"Front. Immunol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1016\/j.biopha.2017.07.102","article-title":"Downregulated NLRP3 and NLRP1 inflammasomes signaling pathways in the development and progression of type 1 diabetes mellitus","volume":"94","author":"Liu","year":"2017","journal-title":"Biomed. Pharmacother."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1590","DOI":"10.1080\/15548627.2017.1341453","article-title":"PTPN22 regulates NLRP3-mediated IL1B secretion in an autophagy-dependent manner","volume":"13","author":"Spalinger","year":"2017","journal-title":"Autophagy"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"e000227","DOI":"10.1136\/bmjdrc-2016-000227","article-title":"Dipeptidyl peptidase-4 inhibition by Saxagliptin prevents inflammation and renal injury by targeting the Nlrp3\/ASC inflammasome","volume":"4","author":"Birnbaum","year":"2016","journal-title":"BMJ Open Diabetes Res. Care"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1038\/ni.1831","article-title":"Thioredoxin-interacting protein links oxidative stress to inflammasome activation","volume":"11","author":"Zhou","year":"2010","journal-title":"Nat. Immunol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1038\/ni.3659","article-title":"Postprandial macrophage-derived IL-1beta stimulates insulin, and both synergistically promote glucose disposal and inflammation","volume":"18","author":"Dror","year":"2017","journal-title":"Nat. Immunol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1038\/s41588-019-0350-x","article-title":"Causal relationships among the gut microbiome, short-chain fatty acids and metabolic diseases","volume":"51","author":"Sanna","year":"2019","journal-title":"Nat. Genet."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1146\/annurev.immunol.021908.132612","article-title":"Immunological and inflammatory functions of the interleukin-1 family","volume":"27","author":"Dinarello","year":"2009","journal-title":"Annu. Rev. Immunol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1038\/378088a0","article-title":"Cloning of a new cytokine that induces IFN-gamma production by T cells","volume":"378","author":"Okamura","year":"1995","journal-title":"Nature"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/S1359-6101(00)00015-0","article-title":"Interleukin-18 is a unique cytokine that stimulates both Th1 and Th2 responses depending on its cytokine milieu","volume":"12","author":"Nakanishi","year":"2001","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.trsl.2016.03.010","article-title":"Interleukin-18-deficient mice develop dyslipidemia resulting in nonalcoholic fatty liver disease and steatohepatitis","volume":"173","author":"Yamanishi","year":"2016","journal-title":"Transl. Res."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"3064","DOI":"10.2337\/db12-1095","article-title":"Interleukin-18 activates skeletal muscle AMPK and reduces weight gain and insulin resistance in mice","volume":"62","author":"Lindegaard","year":"2013","journal-title":"Diabetes"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1007\/s12020-010-9338-0","article-title":"-607 C\/A polymorphism in the promoter of IL-18 gene is associated with 2 h post-loading plasma glucose level in Chinese","volume":"37","author":"Huang","year":"2010","journal-title":"Endocrine"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1111\/j.1464-5491.2007.02109.x","article-title":"Genetic variation in thioredoxin interacting protein (TXNIP) is associated with hypertriglyceridaemia and blood pressure in diabetes mellitus","volume":"24","author":"Vermeulen","year":"2007","journal-title":"Diabet. Med."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1706","DOI":"10.2337\/diabetes.53.7.1706","article-title":"Glucose- and interleukin-1beta-induced beta-cell apoptosis requires Ca2+ influx and extracellular signal-regulated kinase (ERK) 1\/2 activation and is prevented by a sulfonylurea receptor 1\/inwardly rectifying K+ channel 6.2 (SUR\/Kir6.2) selective potassium channel opener in human islets","volume":"53","author":"Maedler","year":"2004","journal-title":"Diabetes"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"50","DOI":"10.3389\/fimmu.2013.00050","article-title":"Mechanisms of disease: Inflammasome activation and the development of type 2 diabetes","volume":"4","author":"Grant","year":"2013","journal-title":"Front. Immunol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"e68","DOI":"10.1016\/j.diabres.2010.11.033","article-title":"Additive hypoglycaemic effect of nateglinide and exogenous glucagon-like peptide-1 in type 2 diabetes","volume":"91","author":"Bell","year":"2011","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"2668","DOI":"10.1001\/jama.2014.15298","article-title":"Metformin in patients with type 2 diabetes and kidney disease: A systematic review","volume":"312","author":"Inzucchi","year":"2014","journal-title":"JAMA"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1016\/j.bcp.2011.11.028","article-title":"DPP-4 inhibitors in the treatment of type 2 diabetes","volume":"83","author":"Duez","year":"2012","journal-title":"Biochem. Pharmacol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1517\/13543780903463862","article-title":"Linagliptin, a xanthine-based dipeptidyl peptidase-4 inhibitor with an unusual profile for the treatment of type 2 diabetes","volume":"19","author":"Deacon","year":"2010","journal-title":"Expert Opin. Investig. Drugs"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1016\/j.ijbiomac.2018.08.004","article-title":"Diarylmethanon, bromophenol and diarylmethane compounds: Discovery of potent aldose reductase, alpha-amylase and alpha-glycosidase inhibitors as new therapeutic approach in diabetes and functional hyperglycemia","volume":"119","author":"Taslimi","year":"2018","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"15324","DOI":"10.1073\/pnas.1100255108","article-title":"Inflammasome is a central player in the induction of obesity and insulin resistance","volume":"108","author":"Stienstra","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1038\/nm.2279","article-title":"The NLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance","volume":"17","author":"Vandanmagsar","year":"2011","journal-title":"Nat. Med."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1212","DOI":"10.1002\/mnfr.201200058","article-title":"Dietary saturated fatty acids prime the NLRP3 inflammasome via TLR4 in dendritic cells-implications for diet-induced insulin resistance","volume":"56","author":"Reynolds","year":"2012","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1038\/nm1415","article-title":"Deficiency of interleukin-18 in mice leads to hyperphagia, obesity and insulin resistance","volume":"12","author":"Netea","year":"2006","journal-title":"Nat. Med."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"11097","DOI":"10.1073\/pnas.0611523104","article-title":"Interleukin-18 controls energy homeostasis by suppressing appetite and feed efficiency","volume":"104","author":"Zorrilla","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1038\/nm1383","article-title":"CNTF reverses obesity-induced insulin resistance by activating skeletal muscle AMPK","volume":"12","author":"Watt","year":"2006","journal-title":"Nat. Med."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1038\/nature05485","article-title":"Inflammation and metabolic disorders","volume":"444","author":"Hotamisligil","year":"2006","journal-title":"Nature"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"958403","DOI":"10.1155\/2010\/958403","article-title":"Circulating levels of interleukin-1 family cytokines in overweight adolescents","volume":"2010","author":"Jung","year":"2010","journal-title":"Mediat. Inflamm."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1186\/1475-2840-10-110","article-title":"Circulating levels of IL-18 are significantly influenced by the IL-18 +183 A\/G polymorphism in coronary artery disease patients with diabetes type 2 and the metabolic syndrome: An observational study","volume":"10","author":"Opstad","year":"2011","journal-title":"Cardiovasc. Diabetol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.jnutbio.2017.04.014","article-title":"Effect of betaine on hepatic insulin resistance through FOXO1-induced NLRP3 inflammasome","volume":"45","author":"Kim","year":"2017","journal-title":"J. Nutr. Biochem."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1563","DOI":"10.1007\/s00394-017-1441-z","article-title":"Mangiferin suppresses endoplasmic reticulum stress in perivascular adipose tissue and prevents insulin resistance in the endothelium","volume":"57","author":"Xu","year":"2018","journal-title":"Eur. J. Nutr."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1016\/j.biopha.2017.03.003","article-title":"Berberine inhibits palmitate-induced NLRP3 inflammasome activation by triggering autophagy in macrophages: A new mechanism linking berberine to insulin resistance improvement","volume":"89","author":"Zhou","year":"2017","journal-title":"Biomed. Pharmacother."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"2116","DOI":"10.2337\/db14-1098","article-title":"Monounsaturated fatty acid-enriched high-fat diets impede adipose NLRP3 inflammasome-mediated IL-1beta secretion and insulin resistance despite obesity","volume":"64","author":"Finucane","year":"2015","journal-title":"Diabetes"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"7283241","DOI":"10.1155\/2017\/7283241","article-title":"Wu-Mei-Wan Reduces Insulin Resistance via Inhibition of NLRP3 Inflammasome Activation in HepG2 Cells","volume":"2017","author":"Yang","year":"2017","journal-title":"Evid. Based Complement. Altern. Med."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"108868","DOI":"10.1016\/j.biopha.2019.108868","article-title":"Carbenoxolone ameliorates insulin sensitivity in obese mice induced by high fat diet via regulating the IkappaB-alpha\/NF-kappaB pathway and NLRP3 inflammasome","volume":"115","author":"Chen","year":"2019","journal-title":"Biomed. Pharmacother."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.cbi.2018.05.004","article-title":"Improvement of hyperglycemia in a murine model of insulin resistance and high glucose- and inflammasome-mediated IL-1beta expressions in macrophages by silymarin","volume":"290","author":"Lu","year":"2018","journal-title":"Chem. Biol. Interact."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"563","DOI":"10.2337\/db07-0698","article-title":"Forkhead transcription factor FoxO1 in adipose tissue regulates energy storage and expenditure","volume":"57","author":"Nakae","year":"2008","journal-title":"Diabetes"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1038\/srep00799","article-title":"Obesity-induced endoplasmic reticulum stress causes chronic inflammation in adipose tissue","volume":"2","author":"Kawasaki","year":"2012","journal-title":"Sci. Rep."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1189\/jlb.0210072","article-title":"Adipose tissue macrophages: Their role in adipose tissue remodeling","volume":"88","author":"Suganami","year":"2010","journal-title":"J. Leukoc. Biol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1016\/j.cell.2010.02.034","article-title":"Endoplasmic reticulum stress and the inflammatory basis of metabolic disease","volume":"140","author":"Hotamisligil","year":"2010","journal-title":"Cell"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1210\/er.2007-0039","article-title":"The unfolded protein response: A pathway that links insulin demand with beta-cell failure and diabetes","volume":"29","author":"Scheuner","year":"2008","journal-title":"Endocr. Rev."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1016\/j.cmet.2012.07.007","article-title":"IRE1alpha induces thioredoxin-interacting protein to activate the NLRP3 inflammasome and promote programmed cell death under irremediable ER stress","volume":"16","author":"Lerner","year":"2012","journal-title":"Cell Metab."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1038\/nrm2199","article-title":"Signal integration in the endoplasmic reticulum unfolded protein response","volume":"8","author":"Ron","year":"2007","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"213","DOI":"10.3389\/fncel.2014.00213","article-title":"A molecular web: Endoplasmic reticulum stress, inflammation, and oxidative stress","volume":"8","author":"Chaudhari","year":"2014","journal-title":"Front. Cell. Neurosci."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"2277","DOI":"10.1089\/ars.2007.1782","article-title":"Endoplasmic reticulum stress and oxidative stress: A vicious cycle or a double-edged sword?","volume":"9","author":"Malhotra","year":"2007","journal-title":"Antioxid. Redox Signal."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1096\/fj.12-226225","article-title":"Dynamin-related protein 1 (Drp1)-mediated diastolic dysfunction in myocardial ischemia-reperfusion injury: Therapeutic benefits of Drp1 inhibition to reduce mitochondrial fission","volume":"28","author":"Sharp","year":"2014","journal-title":"FASEB J."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.mce.2016.06.008","article-title":"Metformin and resveratrol inhibit Drp1-mediated mitochondrial fission and prevent ER stress-associated NLRP3 inflammasome activation in the adipose tissue of diabetic mice","volume":"434","author":"Li","year":"2016","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1038\/nature12480","article-title":"Dietary intervention impact on gut microbial gene richness","volume":"500","author":"Cotillard","year":"2013","journal-title":"Nature"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"2385","DOI":"10.2337\/dc18-0253","article-title":"Gut Microbiota Differs in Composition and Functionality Between Children With Type 1 Diabetes and MODY2 and Healthy Control Subjects: A Case-Control Study","volume":"41","author":"Tinahones","year":"2018","journal-title":"Diabetes Care"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1038\/nature10809","article-title":"Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesity","volume":"482","author":"Elinav","year":"2012","journal-title":"Nature"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"194","DOI":"10.2337\/db12-0420","article-title":"Upregulated NLRP3 inflammasome activation in patients with type 2 diabetes","volume":"62","author":"Lee","year":"2013","journal-title":"Diabetes"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1896","DOI":"10.1038\/s41467-017-01917-2","article-title":"Remodelling of the gut microbiota by hyperactive NLRP3 induces regulatory T cells to maintain homeostasis","volume":"8","author":"Yao","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1016\/j.cell.2011.04.022","article-title":"NLRP6 inflammasome regulates colonic microbial ecology and risk for colitis","volume":"145","author":"Elinav","year":"2011","journal-title":"Cell"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"6519785","DOI":"10.1155\/2017\/6519785","article-title":"Gut Microbiome and Inflammation: A Study of Diabetic Inflammasome-Knockout Mice","volume":"2017","author":"Pahwa","year":"2017","journal-title":"J. Diabetes Res."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1016\/j.it.2004.09.015","article-title":"The chemokine system in diverse forms of macrophage activation and polarization","volume":"25","author":"Mantovani","year":"2004","journal-title":"Trends Immunol."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1016\/j.cell.2018.09.055","article-title":"Microbially Produced Imidazole Propionate Impairs Insulin Signaling through mTORC1","volume":"175","author":"Koh","year":"2018","journal-title":"Cell"}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/9\/12\/850\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:40:49Z","timestamp":1760190049000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/9\/12\/850"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,12,9]]},"references-count":122,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2019,12]]}},"alternative-id":["biom9120850"],"URL":"https:\/\/doi.org\/10.3390\/biom9120850","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,12,9]]}}}