Regulation of system A amino acid transport in 3T3-L1 adipocytes by insulin

被引:26
作者
Su, TZ
Wang, MH
Syu, LJ
Saltiel, AR
Oxender, DL
机构
[1] Parke Davis Pharmaceut Res Div, Dept Mol Biol, Ann Arbor, MI 48105 USA
[2] Parke Davis Pharmaceut Res Div, Dept Cell Biol, Ann Arbor, MI 48105 USA
关键词
D O I
10.1074/jbc.273.6.3173
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The insulin-stimulated uptake of 2-(methylamino) isobutyric acid (MeAIB), a nonmetabolizable substrate for system A, in 3T3-L1 adipocytes was investigated. As cells took on a more adipogenic phenotype, the insulin-stimulated versus the saturable basal MeAIB uptake increased by 5-fold. The induced transport activity showed properties characteristic of system A, with a K-m value of 190 mu M. The half-life of the induced system A activity was independent of de novo mRNA and protein synthesis and was not accelerated by ambient amino acids, therefore, it was mechanistically distinct from the previously described adaptive and hormonal regulation of system A. Inhibition of mitogen-activated protein kinase kinase by PD98059, Ras farnesylation by PD152440 and B581, p70(S6K) by rapamycin, and phosphatidylinositol 3-kinase (PI 3'-K) by wortmannin and LY294002 revealed that only wortmannin and LY294002 inhibited the insulin-induced MeAIB uptake with IC50 values close to that previously reported for inhibition of PI 3'-K. These results suggest that the Ras/mitogen-activated protein kinase and pp70(S6K) insulin signaling pathways are neither required nor sufficient for insulin stimulation of MeAIB uptake, and activation of PI 3'-K or a wortmanninn/LY294002-sensitive pathway may play an important role in regulation of system A transport by insulin in 3T3-L1 cells.
引用
收藏
页码:3173 / 3179
页数:7
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