Aspirin inhibits serine phosphorylation of insulin receptor substrate 1 in growth hormone treated animals.
In this study, we demonstrate that pretreatment with aspirin inhibits GH-induced insulin resistance. GH was observed to lead to serine phosphorylation of IRS-1, a phenomenon which was reversed by aspirin in liver, muscle and WAT in parallel with a reduction in JNK activity. In addition, our data show an impairment of insulin activation in the IR/IRS/PI(3)kinase pathway and a reduction in IRS-1 protein levels in rats treated with GH, which was also reversed in the animals pretreated with aspirin. Overall, these results provide new insights into the mechanism of GH-induced insulin resistance.
Prattali
Raphael R
RR
Departamento de Clínica Médica, FCM, Universidade Estadual de Campinas (UNICAMP), 13081-970 Campinas, SP, Brazil.
Barreiro
Guilherme C
GC
Caliseo
Caio T
CT
Fugiwara
Felipe Y
FY
Ueno
Mirian
M
Prada
Patrícia O
PO
Velloso
Licio A
LA
Saad
Mario J A
MJ
Carvalheira
José B C
JB
D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001241:Aspirin / Q000494:pharmacology*; D013006:Growth Hormone / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology; D055504:Insulin Receptor Substrate Proteins; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009132:Muscles / Q000187:drug effects / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D010768:Phosphoserine / Q000378:metabolism*; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011972:Receptor, Insulin / Q000378:metabolism
D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526296:Irs1 protein, rat; D010750:Phosphoproteins; D016755:Proto-Oncogene Proteins c-jun; D010768:Phosphoserine; D013006:Growth Hormone; D011972:Receptor, Insulin; D048031:JNK Mitogen-Activated Protein Kinases; D001241:Aspirin