Effect of glucagon on insulin receptor substrate-1 (IRS-1) phosphorylation and association with phosphatidylinositol 3-kinase (PI 3-kinase).
In the present study we have examined the levels and phosphorylation state of the insulin receptor and insulin receptor substrate 1 (IRS-1) as well as the association between IRS-1 and phosphatidylinositol 3-kinase (PI 3-kinase) in the liver and muscle of rats treated with glucagon. There was a decrease in the insulin-stimulated receptor and IRS-1 phosphorylation levels which was paralleled by a reduced association between IRS-1 and PI 3-kinase in vivo in the liver and muscle of glucagon-treated rats. These observations suggest that glucagon, probably acting through cAMP, may impair insulin signaling in the three early steps in insulin action after binding.
Saad
M J
MJ
Department of Internal Medicine, FCM, UNICAMP, Cidade Universitária Zeferino Vaz, Campinas, SP, Brazil.
Hartmann
L G
LG
de Carvalho
D S
DS
Galoro
C A
CA
Brenelli
S L
SL
Carvalho
C R
CR
D000818:Animals; D005934:Glucagon / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology*; D055504:Insulin Receptor Substrate Proteins; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases; D010750:Phosphoproteins / Q000187:drug effects / Q000302:isolation & purification / Q000378:metabolism*; D010766:Phosphorylation; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000187:drug effects / Q000378:metabolism*; D019000:Phosphotyrosine; D051381:Rats; D012016:Reference Values; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526296:Irs1 protein, rat; D010750:Phosphoproteins; D019000:Phosphotyrosine; D014443:Tyrosine; D005934:Glucagon; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor)