| http://purl.uniprot.org/citations/19690174 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/19690174 | http://www.w3.org/2000/01/rdf-schema#comment | "Obesity and type 2 diabetes present partially overlapping phenotypes with systemic inflammation as a common feature, raising the hypothesis that elevated cytokine levels may contribute to peripheral insulin resistance as well as the decreased beta cell functional mass observed in type 2 diabetes. In healthy humans, TNF-alpha infusion induces skeletal muscle insulin resistance. We now explore the impact of TNF-alpha on primary beta cell function and the underlying signaling pathways. Human and rat primary beta cells were sorted by FACS and cultured for 24 h +/-20 ng/ml TNF-alpha to explore the impact on apoptosis, proliferation, and short-term insulin secretion (1 h, 2.8 mm glucose followed by 1 h, 16.7 mm glucose at the end of the 24-h culture period) as well as key signaling protein phosphorylation and expression. Prior exposure to TNF-alpha for 24 h inhibits glucose-stimulated insulin secretion from primary beta cells. This is associated with a decrease in glucose-stimulated phosphorylation of key proteins in the insulin signaling pathway including Akt, AS160, and other Akt substrates, ERK as well as the insulin receptor. Strikingly, TNF-alpha treatment decreased IRS-2 protein level by 46 +/-7% versus control, although mRNA expression was unchanged. While TNF-alpha treatment increased MAP4K4 mRNA expression by 33 +/-5%, knockdown of MAP4K4 by siRNA-protected beta cells against the detrimental effects of TNF-alpha on both insulin secretion and signaling. We thus identify MAP4K4 as a key upstream mediator of TNF-alpha action on the beta cell, making it a potential therapeutic target for preservation of beta cell function in type 2 diabetes."xsd:string |
| http://purl.uniprot.org/citations/19690174 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m109.048058"xsd:string |
| http://purl.uniprot.org/citations/19690174 | http://purl.uniprot.org/core/author | "Bouzakri K."xsd:string |
| http://purl.uniprot.org/citations/19690174 | http://purl.uniprot.org/core/author | "Halban P.A."xsd:string |
| http://purl.uniprot.org/citations/19690174 | http://purl.uniprot.org/core/author | "Ribaux P."xsd:string |
| http://purl.uniprot.org/citations/19690174 | http://purl.uniprot.org/core/date | "2009"xsd:gYear |
| http://purl.uniprot.org/citations/19690174 | http://purl.uniprot.org/core/name | "J Biol Chem"xsd:string |
| http://purl.uniprot.org/citations/19690174 | http://purl.uniprot.org/core/pages | "27892-27898"xsd:string |
| http://purl.uniprot.org/citations/19690174 | http://purl.uniprot.org/core/title | "Silencing mitogen-activated protein 4 kinase 4 (MAP4K4) protects beta cells from tumor necrosis factor-alpha-induced decrease of IRS-2 and inhibition of glucose-stimulated insulin secretion."xsd:string |
| http://purl.uniprot.org/citations/19690174 | http://purl.uniprot.org/core/volume | "284"xsd:string |
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