title: Hormetic modulation of hepatic insulin sensitivity by advanced glycation end products.
abstract: Because of the paucity of information regarding metabolic effects of advanced glycation end products (AGEs) on liver, we evaluated effects of AGEs chronic administration in (1) insulin sensitivity; (2) hepatic expression of genes involved in AGEs, glucose and fat metabolism, oxidative stress and inflammation and; (3) hepatic morphology and glycogen content. Rats received intraperitoneally albumin modified (AlbAGE) or not by advanced glycation for 12 weeks. AlbAGE induced whole-body insulin resistance concomitantly with increased hepatic insulin sensitivity, evidenced by activation of AKT, inactivation of GSK3, increased hepatic glycogen content, and decreased expression of gluconeogenesis genes. Additionally there was reduction in hepatic fat content, in expression of lipogenic, pro-inflamatory and pro-oxidative genes and increase in reactive oxygen species and in nuclear expression of NRF2, a transcription factor essential to cytoprotective response. Although considered toxic, AGEs become protective when administered chronically, stimulating AKT signaling, which is involved in cellular defense and insulin sensitivity.
authors.affiliation: Laboratório de Carboidratos e Radioimunoensaios (Laboratório de Investigações Médicas, LIM-18), Faculdade de Medicina, Universidade de São Paulo (FMUSP), Brazil.
authors.forename: Nelly T
authors.initials: NT
authors.lastname: Fabre
authors.affiliation: Laboratório de Carboidratos e Radioimunoensaios (Laboratório de Investigações Médicas, LIM-18), Faculdade de Medicina, Universidade de São Paulo (FMUSP), Brazil.
authors.forename: Karina
authors.initials: K
authors.lastname: Thieme
authors.affiliation: Laboratório de Lípides (Laboratório de Investigações Médicas, LIM-10), FMUSP, Brazil.
authors.forename: Karolline S
authors.initials: KS
authors.lastname: Silva
authors.affiliation: Laboratório de Lípides (Laboratório de Investigações Médicas, LIM-10), FMUSP, Brazil.
authors.forename: Sérgio
authors.initials: S
authors.lastname: Catanozi
authors.affiliation: Laboratório de Carboidratos e Radioimunoensaios (Laboratório de Investigações Médicas, LIM-18), Faculdade de Medicina, Universidade de São Paulo (FMUSP), Brazil.
authors.forename: Ana Mercedes
authors.initials: AM
authors.lastname: Cavaleiro
authors.affiliation: Laboratório de Metabolismo e Endocrinologia, Departamento de Fisiologia e Biofísica, Instituto de Ciências Biomédicas, Universidade de São Paulo, Brazil.
authors.forename: Danilo A C
authors.initials: DA
authors.lastname: Pinto
authors.affiliation: Laboratório de Metabolismo e Endocrinologia, Departamento de Fisiologia e Biofísica, Instituto de Ciências Biomédicas, Universidade de São Paulo, Brazil.
authors.forename: Maristela M
authors.initials: MM
authors.lastname: Okamoto
authors.affiliation: Laboratório de Biologia da Reprodução e Matriz Extracelular, Departamento de Biologia Celular e do Desenvolvimento, Instituto de Ciências Biomédicas, Universidade de São Paulo, Brazil.
authors.forename: Mychel Raony P T
authors.initials: MR
authors.lastname: Morais
authors.affiliation: Laboratório de Controle Cardiorrespiratório, Departamento de Farmacologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, Brazil.
authors.forename: Bárbara
authors.initials: B
authors.lastname: Falquetto
authors.affiliation: Laboratório de Biologia da Reprodução e Matriz Extracelular, Departamento de Biologia Celular e do Desenvolvimento, Instituto de Ciências Biomédicas, Universidade de São Paulo, Brazil.
authors.forename: Telma M
authors.initials: TM
authors.lastname: Zorn
authors.affiliation: Laboratório de Metabolismo e Endocrinologia, Departamento de Fisiologia e Biofísica, Instituto de Ciências Biomédicas, Universidade de São Paulo, Brazil.
authors.forename: Ubiratan F
authors.initials: UF
authors.lastname: Machado
authors.affiliation: Laboratório de Lípides (Laboratório de Investigações Médicas, LIM-10), FMUSP, Brazil.
authors.forename: Marisa
authors.initials: M
authors.lastname: Passarelli
authors.affiliation: Laboratório de Carboidratos e Radioimunoensaios (Laboratório de Investigações Médicas, LIM-18), Faculdade de Medicina, Universidade de São Paulo (FMUSP), Brazil. Electronic address: malugia@lim25.fm.usp.br.
authors.forename: Maria Lúcia
authors.initials: ML
authors.lastname: Correa-Giannella
mesh_terms: D000418:Albumins / Q000494:pharmacology; D000818:Animals; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D005943:Gluconeogenesis / Q000187:drug effects / Q000235:genetics; D017127:Glycation End Products, Advanced / Q000008:administration & dosage / Q000494:pharmacology*; D006003:Glycogen / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta / Q000378:metabolism; D024243:HMGB1 Protein / Q000378:metabolism; D059165:Hormesis / Q000187:drug effects*; D018836:Inflammation Mediators / Q000378:metabolism; D007274:Injections, Intraperitoneal; D007333:Insulin Resistance; D050155:Lipogenesis / Q000187:drug effects / Q000235:genetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008954:Models, Biological; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D010084:Oxidation-Reduction; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D051780:Sterol Regulatory Element Binding Protein 1 / Q000378:metabolism
chemical_list: D000418:Albumins; D017127:Glycation End Products, Advanced; D024243:HMGB1 Protein; D018836:Inflammation Mediators; D051267:NF-E2-Related Factor 2; C495637:Nfe2l2 protein, rat; D017382:Reactive Oxygen Species; D051780:Sterol Regulatory Element Binding Protein 1; D006003:Glycogen; D000071679:Glycogen Synthase Kinase 3 beta; D051057:Proto-Oncogene Proteins c-akt
keywords: AKT; GSK3; Liver; NRF2; RAGE