title: Low salt intake modulates insulin signaling, JNK activity and IRS-1ser307 phosphorylation in rat tissues.
abstract: A severe restriction of sodium chloride intake has been associated with insulin resistance and obesity. The molecular mechanisms by which the low salt diet (LS) can induce insulin resistance have not yet been established. The c-jun N-terminal kinase (JNK) activity has been involved in the pathophysiology of obesity and induces insulin resistance by increasing inhibitory IRS-1(ser307) phosphorylation. In this study we have evaluated the regulation of insulin signaling, JNK activation and IRS-1(ser307) phophorylation in liver, muscle and adipose tissue by immunoprecipitation and immunoblotting in rats fed with LS or normal salt diet (NS) during 9 weeks. LS increased body weight, visceral adiposity, blood glucose and plasma insulin levels, induced insulin resistance and did not change blood pressure. In LS rats a decrease in PI3-K/Akt was observed in liver and muscle and an increase in this pathway was seen in adipose tissue. JNK activity and IRS-1(ser307) phosphorylation were higher in insulin-resistant tissues. In summary, the insulin resistance, induced by LS, is tissue-specific and is accompanied by activation of JNK and IRS-1(ser307) phosphorylation. The impairment of the insulin signaling in these tissues, but not in adipose tissue, may lead to increased adiposity and insulin resistance in LS rats.
authors.affiliation: Departamento de Clínica Médica da Universidade Estadual de Campinas, Campinas, Brazil.
authors.forename: Patrícia Oliveira
authors.initials: PO
authors.lastname: Prada
authors.forename: Michella Soares
authors.initials: MS
authors.lastname: Coelho
authors.forename: Henrique Gottardello
authors.initials: HG
authors.lastname: Zecchin
authors.forename: Miriam Sterman
authors.initials: MS
authors.lastname: Dolnikoff
authors.forename: Alessandra Lia
authors.initials: AL
authors.lastname: Gasparetti
authors.forename: Luzia Naôko Shinohara
authors.initials: LN
authors.lastname: Furukawa
authors.forename: Mario José Abdalla
authors.initials: MJ
authors.lastname: Saad
authors.forename: Joel Claudio
authors.initials: JC
authors.lastname: Heimann
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D015151:Immunoblotting; D047468:Immunoprecipitation; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D055504:Insulin Receptor Substrate Proteins; D007333:Insulin Resistance; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008297:Male; D009132:Muscles / Q000378:metabolism; D009765:Obesity / Q000209:etiology* / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects*; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage*
chemical_list: D001786:Blood Glucose; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526296:Irs1 protein, rat; D010750:Phosphoproteins; D017673:Sodium Chloride, Dietary; D048031:JNK Mitogen-Activated Protein Kinases