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Insulin Resistance Induced by Low Salt Intake is Linked with RAS Activity and Inflammatory Signaling in Tissues
Author(s) -
Coelho Michella Soares,
Negri Heloisa B.,
Oliveira Ivone B.,
Shimizu Maria HM.,
Hirata Aparecida E.,
Casarini Dulce E.,
Prada Patricia O.,
Dolnikoff Miriam S.,
Saad Mario JA.,
Heimann Joel C.
Publication year - 2008
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.22.1_supplement.736.4
Subject(s) - tbars , endocrinology , insulin resistance , medicine , chemistry , oxidative stress , protein kinase b , irs1 , insulin receptor , insulin , phosphorylation , biology , lipid peroxidation , biochemistry
Low salt diet (LS) impairs insulin (INS) signaling and increases angiotensin II (AII) that may enhance JNK and IRS1 ser307 phosphorylation (PHOS), and inflammatory pathways (IP) with consequent reduction in INS action. Objective: To evaluate if losartan (LOS) improves INS resistance induced by LS by decreasing JNK and IRS1 ser307 activity. Methods: Twelve‐week‐old rats were fed a LS (0.15% NaCl) or normal salt diet (NS: 1.3%) since weaning. Groups were studied: LS+LOS (30 mg/kg/day), LS+vehicle, NS+LOS and NS+vehicle. Blood glucose (GLU), plasma INS and TBARS (oxidative stress marker), HOMA index, and tissue AII (immunohistochemistry and HPLC) were evaluated. The steps of INS signaling and IP were determined by immunoblotting. Results (mean±SEM, P<0.05, n = 8): INS, HOMA index and TBARS were higher on LS (INS: 712±60) than on NS (INS: 257±40 pmol/l). GLU and TBARS were lower and INS was higher on LS+LOS (TBARS: 4±0.5) than on LS (TBARS: 6±0.6 nmol/ml). Liver and muscle (M) AII were higher on LS (10±1) compared with NS (2±0.9 cell/mm 2 ). Liver IkBα PHOS was lower on LS (20±2) than on NS (100±±4 %) suggesting an activation of IP on LS. Insulin receptor, PI3K and Akt PHOS (90±4) were higher and JNK (120±3) and IRS1 ser307 (100±6 %) PHOS were lower in the liver of LS+LOS compared to LS. Similar results were observed in M. Conclusions: INS resistance induced by LS is associated with dysregulation of INS signaling, activated IP, and higher tissue AII and TBARS. LOS improves INS signaling by decreasing JNK and IRS1 ser307 PHOS, with consequent reduction in GLU in LS. FAPESP