title: Distinct regulation of IRS proteins in adipose tissue from obese aged and dexamethasone-treated rats.
abstract: In the present study, we investigated the protein levels and phosphorylation status of the insulin receptor and insulin receptor substrates (IRS-1, IRS-2, and IRS-3) as well as their association with PI(3)-kinase in the rat adipose tissue of two models of insulin resistance: dexamethasone treatment and aging. AKT and atypical PKC phosphorylation detection were also performed. Both models showed decreased insulin-induced IRS-1 and IRS-2 tyrosine phosphorylation, accompanied by reduced protein levels of IRS-1 and IRS-2. Nevertheless, IRS-3 protein level was unchanged in aging but increased in dexamethasone-treated rats. PI(3)-kinase association with IRS-1 was reduced in aged rats, whereas dexamethasone-treated rats showed a reduced IRS-2/ PI(3)-kinase association. However, IRS-3 association with PI(3)-kinase was reduced in both models, as well as insulin-induced AKT and PKC phosphorylation. The alterations described in the present study show that the action of insulin is differently impaired depending on the origin of insulin resistance. These differences might be directly linked to the singular metabolic features of the models we tested.
authors.affiliation: Departamento de Fisiologia e Biofísica, Instituto de Ciências Biomédicas, Universidade de São Paulo (USP), São Paulo, SP, Brasil.
authors.forename: Luciana C
authors.initials: LC
authors.lastname: Caperuto
authors.forename: Gabriel F
authors.initials: GF
authors.lastname: Anhê
authors.forename: Angélica M
authors.initials: AM
authors.lastname: Amanso
authors.forename: Luciene M
authors.initials: LM
authors.lastname: Ribeiro
authors.forename: Mayrin C
authors.initials: MC
authors.lastname: Medina
authors.forename: Lilian C
authors.initials: LC
authors.lastname: Souza
authors.forename: Olga M F
authors.initials: OM
authors.lastname: Carvalho
authors.forename: Silvana
authors.initials: S
authors.lastname: Bordin
authors.forename: Mário J A
authors.initials: MJ
authors.lastname: Saad
authors.forename: Carla R O
authors.initials: CR
authors.lastname: Carvalho
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism*; D000375:Aging / Q000502:physiology*; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight; D003907:Dexamethasone / Q000494:pharmacology*; D007328:Insulin / Q000097:blood; D055504:Insulin Receptor Substrate Proteins; D007333:Insulin Resistance; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D009765:Obesity / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011972:Receptor, Insulin / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D000099293:Protein Kinase C-lambda
chemical_list: D001786:Blood Glucose; D003907:Dexamethasone; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D047908:Intracellular Signaling Peptides and Proteins; D007527:Isoenzymes; D019869:Phosphatidylinositol 3-Kinases; D010750:Phosphoproteins; D011493:Protein Kinase C; D011972:Receptor, Insulin; D000099293:Protein Kinase C-lambda; C526296:Irs1 protein, rat; C526299:Irs2 protein, rat; C491584:Irs3 protein, rat