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Angiotensin II and Oxidative Stress Increases JNK and IRS‐1ser307 Activity and Inhibits Insulin Signal Transduction in Rats with Insulin Resistance Induced by Low Salt Intake
Author(s) -
Coelho Michella Soares,
Negri Heloisa B.,
Oliveira Ivone B.,
Ferreira Daniele N.,
Shimizu Maria HM.,
Casarini Dulce E.,
Prada Patricia O.,
Dolnikoff Miriam S.,
Saad Mario JA.,
Heimann Joel C.
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.626.10
Subject(s) - tbars , medicine , endocrinology , insulin resistance , oxidative stress , angiotensin ii , chemistry , losartan , protein kinase b , irs1 , insulin receptor , insulin , signal transduction , receptor , biology , lipid peroxidation , biochemistry
Low salt diet (LS) increases angiotensin II (AII) and oxidative stress (TBARS), which may enhance JNK and IRS1 ser307 phosphorylation (PP) decreasing insulin signaling (INS‐S). Objective To evaluate if losartan (LOS) improves INS resistance by decreasing JNK and IRS1 ser307 PP. Methods Twelve‐week‐old rats were fed a LS (0.15% NaCl) or normal salt diet (NS: 1.3%) since weaning. Groups: LS+LOS (30mg/kg/day), LS+vehicle, NS+LOS and NS+vehicle. Blood pressure (BP), blood glucose (G), plasma INS and TBARS, HOMA, and tissue AII were evaluated. The INS‐S and inflammatory signaling (IS) were determined by Western blot and immunoprecipitation. AT 1 receptor gene expression was determined by RT‐PCR. Results (mean±SEM, P<0.05, n=8) BP and AT 1 did not differ among groups. INS, HOMA and TBARS were higher in LS (INS: 712±60) than in NS (257±40 pmol/l). G and TBARS were lower and INS was higher in LS+LOS (TBARS: 4±0.5) than in LS (6±1 nmol/ml). Liver AII was higher in LS than in NS. INS receptor and Akt PP were higher and JNK (120±3) and IRS1 ser307 PP (100±6 AU) were lower in the liver of LS+LOS compared to LS. IkBα PP was lower in LS (20±2) than in NS (100±4 AU) suggesting an activation of IS in LS. Similar results were observed in the muscle. Conclusions INS resistance induced by LS is associated with alterations in regulation of INS‐S, activated IS, and higher tissue AII and TBARS. In LS, LOS improves INS‐S by decreasing JNK and IRS1 ser307 PP with no change in BP. FAPESP