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Angiotensin II Increases JNK and IRS‐1ser307 Activity via NAD(P)H and Inhibits Insulin Signaling in Rats with Insulin Resistance Induced by Low Salt Diet
Author(s) -
Coelho Michella Soares,
Negri Heloisa B,
Ferreira Daniele N,
Oliveira Ivone B,
Hirata Aparecida E,
Casarini Dulce E,
Prada Patricia O,
Dolnikoff Miriam S,
Saad Mario JA,
Heimann Joel C
Publication year - 2010
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.24.1_supplement.997.5
Subject(s) - medicine , endocrinology , insulin resistance , angiotensin ii , nad+ kinase , chemistry , insulin receptor , receptor , oxidative stress , insulin , downregulation and upregulation , biology , biochemistry , enzyme , gene
Low salt diet (LS) increases angiotensin II (AII), which may enhance JNK and IRS1 ser307 phosphorylation (PP) decreasing insulin signaling (INS‐S). AII stimulate ROS production through activation of NAD(P)H oxidase (NAD). However, whether AII, oxidative stress (OX) and inflammatory signaling (IS) are involved in INS resistance induced by LS is not established. Objective Evaluate if losartan (LOS) improves INS resistance by decreasing OX, JNK and IRS1 ser307 PP. Methods Rats were fed a LS (0.15% NaCl) or normal salt diet (NS: 1.3%) since weaning. Groups: NS, NS+LOS, LS and LS+LOS. NAD activity (subunits p47 and gp91 PHOX ), tissue AII, blood glucose (G), plasma INS, HOMA, INS‐S and IS, AII type 1 (AT 1 ) receptor gene and protein expression were evaluated. Results (P<0.05, n=8): INS level, HOMA index, muscle AII and NAD subunits PP were greater in LS (p47: 10,066±975, gp91: 740±106) than in NS (p47: 5,783±801, gp91: 416±70 AU). G and NAD activity were lower in LS+LOS than in LS. INS receptor and Akt PP were greater and JNK (58±3) and IRS1 ser307 PP (47±3 AU) were lower in the muscle of LS+LOS than in LS. IkB‐α PP was lower in LS (50±3) than in NS (100±3 AU) suggesting an activation of IS in LS. AT 1 did not differ among groups. Conclusions INS resistance induced by LS is associated with alterations in regulation of INS‐S, activated IS (JNK and IkB‐α), and higher tissue AII and NAD activity. In LS, LOS improves INS‐S by decreasing OX, JNK and IRS1 ser307 PP, indicating that LOS may has anti‐inflammatory properties. AII may be a pathway that connects IS, OX and INS resistance in LS. Funded by FAPESP