Down-regulation of different post-receptor signal transduction pathways by chronic insulin stimulation
- VernacularTitle:慢性胰岛素刺激对胰岛素受体后不同信号转导途径的下降调节
- Author:
Li YUAN
;
Ziegler REINHARD
;
Hamann ANDREAS
- Publication Type:Journal Article
- Keywords:
Receptor, insulin;
Signal transduction;
Hyperinsulinism;
Insulin resistance
- From:
Chinese Journal of Endocrinology and Metabolism
1986;0(04):-
- CountryChina
- Language:Chinese
-
Abstract:
Objective To study the effect of chronic insulin stimulation on different signal transduction pathways of insulin post-receptor in a human hepatoma cells line (HepG2). Methods HepG2 cells were incubated in serum-free media in either presence or absence of various concentrations of insulin (0-100 nmol/L) for 16 h before the cells were stimulated with 100 nmol/L insulin for 1 min. Protein levels of insulin receptor ?-subunit (IR?), insulin receptor substrate (IRS)-1, IRS-2, P85 subunit of phosphatidylinositol 3-kinase (PI3K), mitogen activated protein kinase (MAPK) and phosphorylated proteins of MAPK were determined in total cell lysates by Western-immunoblot, and determination of phosphorylated proteins IR?, IRS-1, IRS-2 and interaction of PI3K with IRS-1/-2 were performed by immunoprecipitation. Results Insulin stimulation for 1 min rapidly induced tyrosine phosphorylation of IR?, IRS-1 and IRS-2 and phosphorylation of MAPK, which in turn, resulted in binding of P85 with IRS-1/-2 and activation of MAPK. After 100 nmol/L insulin treatment for 16 h, there was a more marked reduction in the phosphorylations of IR?,IRS1andIRS2inHepG2 cells, reaching 22.2% (P
