Low salt intake modulates insulin signaling, JNK activity and IRS-1ser307 phosphorylation in rat tissues.
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.
Prada
Patrícia Oliveira
PO
Departamento de Clínica Médica da Universidade Estadual de Campinas, Campinas, Brazil.
Coelho
Michella Soares
MS
Zecchin
Henrique Gottardello
HG
Dolnikoff
Miriam Sterman
MS
Gasparetti
Alessandra Lia
AL
Furukawa
Luzia Naôko Shinohara
LN
Saad
Mario José Abdalla
MJ
Heimann
Joel Claudio
JC
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*
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