Aspirin inhibits serine phosphorylation of IRS-1 in muscle and adipose tissue of septic rats.
Whole body insulin resistance has been demonstrated in septic patients and in infected animals. In this study, we demonstrate that sepsis induces insulin resistance and that pretreatment with aspirin inhibits sepsis-induced insulin resistance. Sepsis was observed to lead to serine phosphorylation of IRS-1, a phenomenon which was reversed by aspirin in muscle and WAT, in parallel with a reduction in JNK activity. In addition, our data show an impairment of insulin activation of IR and IRS-1 tyrosine phosphorylation in septic rats and, consistent with the reduction of IRS-1 serine phosphorylation observed in septic animals pretreated with aspirin, there was an increase in IRS-1 protein levels and tyrosine phosphorylation in muscle and WAT. Overall, these results provide important new insights into the mechanism of sepsis-induced insulin resistance.
Barreiro
Guilherme C
GC
Departamento de Clínica Médica, FCM, Universidade Estadual de Campinas (UNICAMP), Campinas, SP, Brazil.
Prattali
Raphael R
RR
Caliseo
Caio T
CT
Fugiwara
Felipe Y
FY
Ueno
Mirian
M
Prada
Patrícia O
PO
Velloso
Lício A
LA
Saad
Mario J A
MJ
Carvalheira
José B C
JB
D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D001241:Aspirin / Q000494:pharmacology*; D055504:Insulin Receptor Substrate Proteins; D007333:Insulin Resistance; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D018805:Sepsis / Q000378:metabolism*; D012694:Serine / Q000378:metabolism*
D055504:Insulin Receptor Substrate Proteins; C526296:Irs1 protein, rat; D010750:Phosphoproteins; D012694:Serine; D001241:Aspirin