Phosphoinositide 3-kinase is required for insulin-induced but not for growth hormone- or hyperosmolarity-induced glucose uptake in 3T3-L1 adipocytes.
Phosphoinositide 3-kinase is required for insulin-induced but not for growth hormone- or hyperosmolarity-induced glucose uptake in 3T3-L1 adipocytes.
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磷酸肌醇 3-激酶是 3T3-L1 脂肪细胞中胰岛素诱导的葡萄糖摄取所必需的，但生长激素或高渗透压诱导的葡萄糖摄取则不需要。
作者：
H. Sakaue;W. Ogawa;M. Takata;S. Kuroda;Kei Kotani;M. Matsumoto;M. Sakaue;S. Nishio;H. Ueno;M. Kasuga
利用编码多种优势负性蛋白的重组腺病毒载体，研究了3T3-L1脂肪细胞葡萄糖摄取的调控机制。编码不结合110 kDa催化亚基的磷脂酰肌醇(PI)3-激酶调节亚基突变的病毒(Delta P85)感染后，以病毒剂量依赖的方式抑制胰岛素诱导的由磷酸酪氨酸抗体和葡萄糖摄取共沉淀的PI 3-激酶活性的增加。将Asp57替换为酪氨酸(RAS57Y)的显性负Ras突变体(RAS57Y)或缺乏鸟核苷酸交换活性的显性负SOS突变体(Delta SOS)的过表达可消除胰岛素诱导的丝裂原活化蛋白激酶活性的增加，但对PI 3-激酶活性或葡萄糖摄取没有影响。虽然生长激素和300 mM山梨醇的高渗透压都能促进葡萄糖的摄取和葡萄糖转运体(GLUT)4的转位，但这些刺激很少或根本没有引起PI3-K活性与酪氨酸磷酸化蛋白的关联。过表达Delta P85或用PI 3-激酶活性抑制剂Wortmannin处理细胞，对GH或高渗刺激的葡萄糖摄取或GLUT4转位均无影响。此外，Delta SOS或RAC17N的过表达也不影响这些刺激引起的葡萄糖摄取的增加。丝氨酸/苏氨酸激酶Akt是一种结构性活性突变体，以前被证明可以刺激葡萄糖摄取，它被胰岛素、生长激素和高渗透压激活，分别是基础水平的约4倍、约2.1倍和约2.3倍。这些结果表明，胰岛素诱导的3T3-L1脂肪细胞的葡萄糖摄取不依赖于PI 3-激酶，而生长激素或高渗透压诱导的葡萄糖摄取不需要RAS或RAC。
The(1) regulatory mechanism of glucose uptake in 3T3-L1 adipocytes was investigated with the use of recombinant adenovirus vectors encoding various dominant negative proteins. Infection with a virus encoding a mutant regulatory subunit of phosphoinositide (PI) 3-kinase that does not bind the 110-kDa catalytic subunit (delta p85) inhibited the insulin-induced increase in PI 3-kinase activity co-precipitated by antibodies to phosphotyrosine and glucose uptake in a virus dose-dependent manner. Overexpression of a dominant negative RAS mutant in which Asp57 is replaced with tyrosine (RAS57Y) or of a dominant negative SOS mutant that lacks guanine nucleotide exchange activity (delta SOS) abolished the insulin-induced increase in mitogen-activated protein kinase activity, but had no effect on PI 3-kinase activity or glucose uptake. Although GH and hyperosmolarity attributable to 300 mM sorbitol each promoted glucose uptake and translocation of glucose transporter (GLUT)4 to an extent comparable to that of insulin, these stimuli triggered little or no association of PI 3-kinase activity with tyrosine-phosphorylated proteins. Overexpression of delta p85 or treatment of cells with wortmannin, an inhibitor of PI 3-kinase activity, had no effect on glucose uptake or translocation of GLUT4 stimulated by GH or hyperosmolarity. Moreover, overexpression of delta SOS or RAC17N also did not affect the increase in glucose uptake induced by these stimuli. A serine/threonine kinase Akt, a constitutively active mutant of which was previously shown to stimulate glucose uptake, is activated by insulin, GH, and hyperosmolarity to approximately 4-fold, approximately 2.1-fold, and approximately 2.3-fold over basal level, respectively. These results suggest that insulin-induced but neither GH- or hyperosmolarity-induced glucose uptake is PI 3-kinase-dependent, and neither RAS nor RAC is required for glucose uptake induced by these stimuli in 3T3-L1 adipocytes.
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DOI：
10.1073/pnas.82.10.3400
发表时间：
1985-01-01
影响因子：
11.1
作者：
TANAKA, T;SLAMON, DJ;CLINE, MJ
通讯作者：
CLINE, MJ
生长激素刺激 3T3-F442A 成纤维细胞中 MAP 激酶活性。
DOI：
--
发表时间：
1992
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Campbell,GS;Pang,L;Miyasaka,T;Saltiel,AR;Carter-Su,C
通讯作者：
Carter-Su,C
Raf-1 在介导胰岛素刺激的葡萄糖转运的不同信号通路中的作用。
DOI：
--
发表时间：
1994
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Fingar,DC;Birnbaum,MJ
通讯作者：
Birnbaum,MJ
脂肪细胞中生长激素的类胰岛素作用的细胞机制。
DOI：
10.1042/bj2820099
发表时间：
1992
期刊：
The Biochemical journal
影响因子：
--
作者：
Tanner,JW;Leingang,KA;Mueckler,MM;Glenn,KC
通讯作者：
Glenn,KC
p21ras 在 3T3-L1 脂肪细胞中胰岛素刺激的葡萄糖转运中的作用。
DOI：
--
发表时间：
1994
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Hausdorff,SF;Frangioni,JV;Birnbaum,MJ
通讯作者：
Birnbaum,MJ