{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T01:23:14Z","timestamp":1792545794757,"version":"4.5.0"},"reference-count":60,"publisher":"Elsevier BV","issue":"6","license":[{"start":{"date-parts":[[2015,12,1]],"date-time":"2015-12-01T00:00:00Z","timestamp":1448928000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2015,12,1]],"date-time":"2015-12-01T00:00:00Z","timestamp":1448928000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Medical Hypotheses"],"published-print":{"date-parts":[[2015,12]]},"DOI":"10.1016\/j.mehy.2015.08.019","type":"journal-article","created":{"date-parts":[[2015,9,6]],"date-time":"2015-09-06T07:01:38Z","timestamp":1441522898000},"page":"997-1001","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":29,"title":["Inflammasome, mTORC1 activation, and metabolic derangement contribute to the susceptibility of diabetics to infections"],"prefix":"10.1016","volume":"85","author":[{"given":"Teresa","family":"Krakauer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.mehy.2015.08.019_b0005","doi-asserted-by":"crossref","first-page":"510","DOI":"10.2337\/diacare.26.2.510","article-title":"Quantifying the risk of infectious diseases for people with diabetes","volume":"26","author":"Shah","year":"2003","journal-title":"Diabetes Care"},{"key":"10.1016\/j.mehy.2015.08.019_b0010","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1086\/431587","article-title":"Increased risk of common infections in patients with type 1 and type 2 diabetes mellitus","volume":"41","author":"Muller","year":"2005","journal-title":"Clin Infect Dis"},{"key":"10.1016\/j.mehy.2015.08.019_b0015","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1086\/519939","article-title":"Convergence of the tuberculosis and diabetes epidemics: renewal of old acquaintances","volume":"45","author":"Restrepo","year":"2007","journal-title":"Clin Infect Dis"},{"key":"10.1016\/j.mehy.2015.08.019_b0020","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1056\/NEJMoa0706245","article-title":"Effect of a multifactorial intervention on mortality in type 2 diabetes","volume":"358","author":"Gaede","year":"2008","journal-title":"N Engl J Med"},{"key":"10.1016\/j.mehy.2015.08.019_b0025","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1016\/S1473-3099(09)70282-8","article-title":"Tuberculosis and diabetes mellitus: convergence of two epidemics","volume":"9","author":"Dooley","year":"2009","journal-title":"Lancet Infect Dis"},{"key":"10.1016\/j.mehy.2015.08.019_b0030","doi-asserted-by":"crossref","first-page":"S62","DOI":"10.2337\/dc10-S062","article-title":"Diagnosis and classification of diabetes mellitus","volume":"33","author":"American Diabetes Association","year":"2010","journal-title":"Diabetes Care"},{"key":"10.1016\/j.mehy.2015.08.019_b0035","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":"Nature Rev Immunol"},{"key":"10.1016\/j.mehy.2015.08.019_b0040","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/j.it.2011.05.004","article-title":"NLRP3 inflammasomes link inflammation and metabolic disease","volume":"32","author":"De Nardo","year":"2011","journal-title":"Trends Immunol"},{"key":"10.1016\/j.mehy.2015.08.019_b0045","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1038\/ni.2028","article-title":"Dampening insulin signaling by an NLRP3 \u2018meta-flammasome\u2019","volume":"12","author":"Choi","year":"2011","journal-title":"Nature Immunol"},{"key":"10.1016\/j.mehy.2015.08.019_b0050","doi-asserted-by":"crossref","first-page":"2596","DOI":"10.1096\/fj.09-151340","article-title":"JNK1 and IKKbeta: molecular links between obesity and metabolic dysfunction","volume":"24","author":"Solinas","year":"2010","journal-title":"FASEB J"},{"key":"10.1016\/j.mehy.2015.08.019_b0055","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":"10.1016\/j.mehy.2015.08.019_b0060","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1038\/nature01137","article-title":"A central role for JNK in obesity and insulin resistance","volume":"420","author":"Hirosumi","year":"2002","journal-title":"Nature"},{"key":"10.1016\/j.mehy.2015.08.019_b0065","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/S1097-2765(02)00599-3","article-title":"The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta","volume":"10","author":"Martinon","year":"2002","journal-title":"Mol cell"},{"key":"10.1016\/j.mehy.2015.08.019_b0070","doi-asserted-by":"crossref","first-page":"781","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":"10.1016\/j.mehy.2015.08.019_b0075","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1111\/j.1600-065X.2011.01046.x","article-title":"The inflammasome: an integrated view","volume":"243","author":"Gross","year":"2011","journal-title":"Immunol Rev"},{"key":"10.1016\/j.mehy.2015.08.019_b0080","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1038\/ni.1636","article-title":"The NALP3 inflammasome is involved in the innate immune response to amyloid-beta","volume":"9","author":"Halle","year":"2008","journal-title":"Nat Immunol"},{"key":"10.1016\/j.mehy.2015.08.019_b0085","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":"10.1016\/j.mehy.2015.08.019_b0090","doi-asserted-by":"crossref","first-page":"1517","DOI":"10.1056\/NEJMoa065213","article-title":"Interleukin-1-receptor antagonist in type 2 diabetes mellitus","volume":"356","author":"Larsen","year":"2007","journal-title":"N Engl J Med"},{"key":"10.1016\/j.mehy.2015.08.019_b0095","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1038\/nrm3025","article-title":"MTOR: from growth signal integration to cancer, diabetes and ageing","volume":"12","author":"Zoncu","year":"2011","journal-title":"Nat Rev Mol Cell Biol"},{"key":"10.1016\/j.mehy.2015.08.019_b0100","doi-asserted-by":"crossref","first-page":"1600","DOI":"10.2337\/db06-1016","article-title":"The mammalian target of rapamycin pathway regulates nutrient-sensitive glucose uptake in man","volume":"56","author":"Krebs","year":"2007","journal-title":"Diabetes"},{"key":"10.1016\/j.mehy.2015.08.019_b0105","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1007\/s10059-013-0138-2","article-title":"Nutrient regulation of the mTOR complex 1 signaling pathway","volume":"35","author":"Kim","year":"2013","journal-title":"Mol Cells"},{"key":"10.1016\/j.mehy.2015.08.019_b0110","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1038\/nature06639","article-title":"Autophagy fights disease through cellular self-digestion","volume":"451","author":"Mizushima","year":"2008","journal-title":"Nature"},{"key":"10.1016\/j.mehy.2015.08.019_b0115","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1038\/414799a","article-title":"Insulin signalling and the regulation of glucose and lipid metabolism","volume":"414","author":"Saltiel","year":"2001","journal-title":"Nature"},{"key":"10.1016\/j.mehy.2015.08.019_b0120","doi-asserted-by":"crossref","first-page":"2282","DOI":"10.1074\/jbc.M412179200","article-title":"Insulin receptor substrate-2 proteasomal degradation mediated by a mammalian target of rapamycin (mTOR)-induced negative feedback down-regulates protein kinase B-mediated signaling pathway in beta-cells","volume":"280","author":"Briaud","year":"2005","journal-title":"J Biol Chem"},{"key":"10.1016\/j.mehy.2015.08.019_b0125","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1126\/science.1104345","article-title":"Type 2 diabetes \u2013 a matter of beta-cell life and death?","volume":"307","author":"Rhodes","year":"2005","journal-title":"Science"},{"key":"10.1016\/j.mehy.2015.08.019_b0130","doi-asserted-by":"crossref","first-page":"1642","DOI":"10.1126\/science.1120781","article-title":"The kinase LKB1 mediates glucose homeostasis in liver and therapeutic effects of metformin","volume":"310","author":"Shaw","year":"2005","journal-title":"Science"},{"key":"10.1016\/j.mehy.2015.08.019_b0135","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1146\/annurev.immunol.20.083001.084359","article-title":"Innate Immune recognition","volume":"20","author":"Janeway","year":"2002","journal-title":"Annu Rev Immunol"},{"key":"10.1016\/j.mehy.2015.08.019_b0140","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1016\/j.cell.2010.01.022","article-title":"Pattern recognition receptors and inflammation","volume":"140","author":"Takeuchi","year":"2010","journal-title":"Cell"},{"key":"10.1016\/j.mehy.2015.08.019_b0145","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1111\/j.1752-8062.2008.00026.x","article-title":"Use of salsalate to target inflammation in the treatment of insulin resistance and type 2 diabetes","volume":"1","author":"Goldfine","year":"2008","journal-title":"Clin Transl Sci"},{"key":"10.1016\/j.mehy.2015.08.019_b0150","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1016\/j.immuni.2009.02.005","article-title":"The NLRP3 inflammasome mediates in vivo innate immunity to influenza A virus through recognition of viral RNA","volume":"30","author":"Allen","year":"2009","journal-title":"Immunity"},{"key":"10.1016\/j.mehy.2015.08.019_b0155","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1038\/nature06664","article-title":"The inflammasome recognizes cytosolic microbial and host DNA and triggers an innate immune response","volume":"452","author":"Muruve","year":"2008","journal-title":"Nature"},{"key":"10.1016\/j.mehy.2015.08.019_b0160","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.mib.2012.11.008","article-title":"Inflammasomes and host defenses against bacterial infections","volume":"16","author":"Vladimer","year":"2013","journal-title":"Curr Opin Micro"},{"key":"10.1016\/j.mehy.2015.08.019_b0165","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1093\/jb\/mvm032","article-title":"Antiviral signaling through pattern recognition receptors","volume":"141","author":"Kawai","year":"2007","journal-title":"J Biochem"},{"key":"10.1016\/j.mehy.2015.08.019_b0170","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1038\/nri2161","article-title":"Unveiling the roles of autophagy in innate and adaptive immunity","volume":"7","author":"Levine","year":"2007","journal-title":"Nature Rev Immunol"},{"key":"10.1016\/j.mehy.2015.08.019_b0175","first-page":"123","article-title":"Autophagy in MHC class II presentation of endogenous antigens","volume":"335","author":"Gannage","year":"2009","journal-title":"Curr Top Microbiol Immunol"},{"key":"10.1016\/j.mehy.2015.08.019_b0180","series-title":"Fundamental immunology","first-page":"783","article-title":"TNF family cytokines, chemokines and other pro- or anti-inflammatory cytokines","author":"Krakauer","year":"1998"},{"key":"10.1016\/j.mehy.2015.08.019_b0185","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1210\/en.2006-0692","article-title":"Interleukin 1beta-induced insulin resistance in adipocytes through down-regulation of insulin receptor substrate 1 expression","volume":"148","author":"Jager","year":"2007","journal-title":"Endocrinology"},{"key":"10.1016\/j.mehy.2015.08.019_b0190","doi-asserted-by":"crossref","first-page":"4854","DOI":"10.1073\/pnas.91.11.4854","article-title":"Tumor necrosis factor alpha inhibits signaling from the insulin receptor","volume":"91","author":"Hotamisligil","year":"1994","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1016\/j.mehy.2015.08.019_b0195","doi-asserted-by":"crossref","first-page":"249","DOI":"10.2337\/db09-0801","article-title":"Hyperglycemia-induced reactive oxygen species increase expression of the receptor for advanced glycation end products (RAGE) and RAGE ligands","volume":"59","author":"Yao","year":"2010","journal-title":"Diabetes"},{"key":"10.1016\/j.mehy.2015.08.019_b0200","doi-asserted-by":"crossref","first-page":"106","DOI":"10.3389\/fendo.2013.00105","article-title":"RAGE-mediated inflammation, Type 2 diabetes, and diabetic vascular complication","volume":"4","author":"Yamamoto","year":"2013","journal-title":"Front Endocrinol"},{"key":"10.1016\/j.mehy.2015.08.019_b0205","doi-asserted-by":"crossref","first-page":"1058","DOI":"10.1161\/CIRCRESAHA.110.223545","article-title":"Oxidative stress and diabetic complications","volume":"107","author":"Giacco","year":"2010","journal-title":"Cir Res"},{"key":"10.1016\/j.mehy.2015.08.019_b0210","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1038\/nature09663","article-title":"A role for mitochondria in NLRP3 inflammasome activation","volume":"469","author":"Zhou","year":"2011","journal-title":"Nature"},{"key":"10.1016\/j.mehy.2015.08.019_b0215","doi-asserted-by":"crossref","first-page":"3015","DOI":"10.1172\/JCI28898","article-title":"TLR4 links innate immunity and fatty acid-induced insulin resistance","volume":"116","author":"Shi","year":"2006","journal-title":"J Clin Invest"},{"key":"10.1016\/j.mehy.2015.08.019_b0220","doi-asserted-by":"crossref","first-page":"30299","DOI":"10.1074\/jbc.M607007200","article-title":"Endoplasmic reticulum stress triggers autophagy","volume":"281","author":"Yorimitsu","year":"2006","journal-title":"J Biol Chem"},{"key":"10.1016\/j.mehy.2015.08.019_b0225","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1111\/j.1463-1326.2012.01657.x","article-title":"Metabolic stress, IAPP and islet amyloid","volume":"14","author":"Montane","year":"2012","journal-title":"Diabetes Obes Metab"},{"key":"10.1016\/j.mehy.2015.08.019_b0230","doi-asserted-by":"crossref","first-page":"1733","DOI":"10.2337\/diab.46.11.1733","article-title":"Relation between antioxidant enzyme gene expression and antioxidative defense status of insulin-producing cells","volume":"46","author":"Tiedge","year":"1997","journal-title":"Diabetes"},{"key":"10.1016\/j.mehy.2015.08.019_b0235","doi-asserted-by":"crossref","first-page":"S119","DOI":"10.2337\/diabetes.53.2007.S119","article-title":"Beta-cell glucose toxicity, lipotoxicity, and chronic oxidative stress in type 2 diabetes","volume":"53","author":"Robertson","year":"2004","journal-title":"Diabetes"},{"key":"10.1016\/j.mehy.2015.08.019_b0240","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":"10.1016\/j.mehy.2015.08.019_b0245","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1111\/j.1600-065X.2011.01044.x","article-title":"Caspase-1-induced pyroptotic cell death","volume":"243","author":"Miao","year":"2011","journal-title":"Immunol Review"},{"key":"10.1016\/j.mehy.2015.08.019_b0250","doi-asserted-by":"crossref","first-page":"1054","DOI":"10.4161\/auto.28528","article-title":"A nonapoptotic role for CASP2\/caspase 2: modulation of autophagy","volume":"10","author":"Tiwari","year":"2014","journal-title":"Autophagy"},{"key":"10.1016\/j.mehy.2015.08.019_b0255","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1089\/dna.2014.2752","article-title":"Autophagy and inflammasome interplay","volume":"34","author":"Martins","year":"2015","journal-title":"DNA Cell Biol"},{"key":"10.1016\/j.mehy.2015.08.019_b0260","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1038\/ni.1980","article-title":"Autophagy proteins regulate innate immune responses by inhibiting the release of mitochondrial DNA mediated by the NALP3 inflammasome","volume":"12","author":"Nakahira","year":"2011","journal-title":"Nat Immunol"},{"key":"10.1016\/j.mehy.2015.08.019_b0265","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1126\/science.1103966","article-title":"Autophagy defends cells against invading group A Streptococcus","volume":"306","author":"Nakagawa","year":"2004","journal-title":"Science"},{"key":"10.1016\/j.mehy.2015.08.019_b0270","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1016\/j.cell.2004.11.038","article-title":"Autophagy is a defense mechanism inhibiting BCG and Mycobacterium tuberculosis survival in infected macrophages","volume":"119","author":"Gutierrez","year":"2004","journal-title":"Cell"},{"key":"10.1016\/j.mehy.2015.08.019_b0275","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1038\/ni.2215","article-title":"Activation of autophagy by inflammatory signals limits IL-1\u03b2 production by targeting ubiquitinated inflammasomes for destruction","volume":"13","author":"Shi","year":"2012","journal-title":"Nature Immunol"},{"key":"10.1016\/j.mehy.2015.08.019_b0280","doi-asserted-by":"crossref","first-page":"68","DOI":"10.3389\/fendo.2013.00068","article-title":"Diabetes alters activation and repression of pro- and anti-inflammatory signaling pathways in the vasculature","volume":"4","author":"Di Marco","year":"2013","journal-title":"Front Endocrinol"},{"key":"10.1016\/j.mehy.2015.08.019_b0285","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1210\/jc.2007-1817","article-title":"Clinical review: the role of advanced glycation end products in progression and complications of diabetes","volume":"93","author":"Goh","year":"2008","journal-title":"J Clin Endocrinol Metab"},{"key":"10.1016\/j.mehy.2015.08.019_b0290","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1016\/j.atherosclerosis.2006.09.016","article-title":"Short-term high glucose exposure induces monocyte-endothelial cells adhesion and transmigration by increasing VCAM-1 and MCP-1 expression in human aortic endothelial cells","volume":"193","author":"Piga","year":"2007","journal-title":"Atherosclerosis"},{"key":"10.1016\/j.mehy.2015.08.019_b0295","doi-asserted-by":"crossref","first-page":"2262","DOI":"10.1161\/01.CIR.96.7.2262","article-title":"Advanced glycation end product (AGE)-mediated induction of tissue factor in cultured endothelial cells is dependent on RAGE","volume":"96","author":"Bierhaus","year":"1997","journal-title":"Circulation"},{"key":"10.1016\/j.mehy.2015.08.019_b0300","doi-asserted-by":"crossref","first-page":"2409","DOI":"10.1084\/jem.20081188","article-title":"Transient high glucose causes persistent epigenetic changes and altered gene expression during subsequent normoglycemia","volume":"205","author":"El-Osta","year":"2008","journal-title":"J Exp Med"}],"container-title":["Medical Hypotheses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0306987715003254?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0306987715003254?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,5]],"date-time":"2025-10-05T19:16:32Z","timestamp":1759691792000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0306987715003254"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,12]]},"references-count":60,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2015,12]]}},"alternative-id":["S0306987715003254"],"URL":"https:\/\/doi.org\/10.1016\/j.mehy.2015.08.019","relation":{},"ISSN":["0306-9877"],"issn-type":[{"value":"0306-9877","type":"print"}],"subject":[],"published":{"date-parts":[[2015,12]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Inflammasome, mTORC1 activation, and metabolic derangement contribute to the susceptibility of diabetics to infections","name":"articletitle","label":"Article Title"},{"value":"Medical Hypotheses","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.mehy.2015.08.019","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"Published by Elsevier Ltd.","name":"copyright","label":"Copyright"}]}}