Infliximab restores glucose Homeostasis in an animal model of diet-induced obesity and diabetes

dc.creatorAraujo, EP
dc.creatorDe Souza, CT
dc.creatorUeno, M
dc.creatorCintra, DE
dc.creatorBertolo, MB
dc.creatorCarvalheira, JB
dc.creatorSaad, MJ
dc.creatorVelloso, LA
dc.date2007
dc.dateDEC
dc.date2014-11-19T16:24:37Z
dc.date2015-11-26T16:28:31Z
dc.date2014-11-19T16:24:37Z
dc.date2015-11-26T16:28:31Z
dc.date.accessioned2018-03-28T23:09:32Z
dc.date.available2018-03-28T23:09:32Z
dc.identifierEndocrinology. Endocrine Soc, v. 148, n. 12, n. 5991, n. 5997, 2007.
dc.identifier0013-7227
dc.identifierWOS:000250967000042
dc.identifier10.1210/en.2007-0132
dc.identifierhttp://www.repositorio.unicamp.br/jspui/handle/REPOSIP/60172
dc.identifierhttp://www.repositorio.unicamp.br/handle/REPOSIP/60172
dc.identifierhttp://repositorio.unicamp.br/jspui/handle/REPOSIP/60172
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1269486
dc.descriptionTNF-alpha plays an important role in obesity-linked insulin resistance and diabetes mellitus by activating at least two serine kinases capable of promoting negative regulation of key elements of the insulin signaling pathway. Pharmacological inhibition of TNF-alpha is currently in use for the treatment of rheumatoid and psoriatic arthritis, and some case reports have shown clinical improvement of diabetes in patients treated with the TNF-alpha blocking monoclonal antibody infliximab. The objective of this study was to evaluate the effect of infliximab on glucose homeostasis and insulin signal transduction in an animal model of diabetes. Diabetes was induced in Swiss mice by a fat-rich diet. Glucose and insulin homeostasis were evaluated by glucose and insulin tolerance tests and by the hyperinsulinemic-euglycemic clamp. Signal transduction was evaluated by immunoprecipitation and immunoblotting assays. Short-term treatment with infliximab rapidly reduced blood glucose and insulin levels and glucose and insulin areas under the curve during a glucose tolerance test. Furthermore, infliximab increased the glucose decay constant during an insulin tolerance test and promoted a significant increase in glucose infusion rate during a hyperinsulinemic-euglycemic clamp. In addition, the clinical outcomes were accompanied by improved insulin signal transduction in muscle, liver, and hypothalamus, as determined by the evaluation of insulin-induced insulin receptor, insulin receptor substrate-1, and receptor substrate-2 tyrosine phosphorylation and Akt and forkhead box protein O1 serine phosphorylation. Thus, pharmacological inhibition of TNF-alpha may be an attractive approach to treat severely insulin-resistant patients with type 2 diabetes mellitus.
dc.descriptiono TEXTO COMPLETO DESTE ARTIGO, ESTARÁ DISPONÍVEL À PARTIR DE AGOSTO DE 2015.
dc.description148
dc.description12
dc.description5991
dc.description5997
dc.languageen
dc.publisherEndocrine Soc
dc.publisherChevy Chase
dc.publisherEUA
dc.relationEndocrinology
dc.relationEndocrinology
dc.rightsembargo
dc.sourceWeb of Science
dc.subjectNecrosis-factor-alpha
dc.subjectInduced Insulin-resistance
dc.subjectTnf-alpha
dc.subjectRheumatoid-arthritis
dc.subjectAntibody Infliximab
dc.subjectHepatic Steatosis
dc.subjectKinase-activity
dc.subjectAdipose-tissue
dc.subjectReceptor
dc.subjectInflammation
dc.titleInfliximab restores glucose Homeostasis in an animal model of diet-induced obesity and diabetes
dc.typeArtículos de revistas


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