Bogan J S, Lodish H F
Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142-1479, USA.
J Cell Biol. 1999 Aug 9;146(3):609-20. doi: 10.1083/jcb.146.3.609.
Insulin stimulates adipose cells both to secrete proteins and to translocate the GLUT4 glucose transporter from an intracellular compartment to the plasma membrane. We demonstrate that whereas insulin stimulation of 3T3-L1 adipocytes has no effect on secretion of the alpha3 chain of type VI collagen, secretion of the protein hormone adipocyte complement related protein of 30 kD (ACRP30) is markedly enhanced. Like GLUT4, regulated exocytosis of ACRP30 appears to require phosphatidylinositol-3-kinase activity, since insulin-stimulated ACRP30 secretion is blocked by pharmacologic inhibitors of this enzyme. Thus, 3T3-L1 adipocytes possess a regulated secretory compartment containing ACRP30. Whether GLUT4 recycles to such a compartment has been controversial. We present deconvolution immunofluorescence microscopy data demonstrating that the subcellular distributions of ACRP30 and GLUT4 are distinct and nonoverlapping; in contrast, those of GLUT4 and the transferrin receptor overlap. Together with supporting evidence that GLUT4 does not recycle to a secretory compartment via the trans-Golgi network, we conclude that there are at least two compartments that undergo insulin-stimulated exocytosis in 3T3-L1 adipocytes: one for ACRP30 secretion and one for GLUT4 translocation.
胰岛素刺激脂肪细胞分泌蛋白质，并使GLUT4葡萄糖转运蛋白从细胞内区室转运至质膜。我们证明，虽然胰岛素刺激3T3-L1脂肪细胞对VI型胶原蛋白α3链的分泌没有影响，但30kD蛋白质激素脂肪细胞补体相关蛋白（ACRP30）的分泌却显著增强。与GLUT4一样，ACRP30的调节性胞吐作用似乎需要磷脂酰肌醇-3-激酶活性，因为胰岛素刺激的ACRP30分泌会被该酶的药理抑制剂阻断。因此，3T3-L1脂肪细胞拥有一个含有ACRP30的调节性分泌区室。GLUT4是否循环至这样一个区室一直存在争议。我们提供了去卷积免疫荧光显微镜数据，表明ACRP30和GLUT4的亚细胞分布是不同且不重叠的；相反，GLUT4和转铁蛋白受体的亚细胞分布是重叠的。结合支持GLUT4不会通过反式高尔基体网络循环至分泌区室的证据，我们得出结论，在3T3-L1脂肪细胞中至少有两个区室经历胰岛素刺激的胞吐作用：一个用于ACRP30分泌，一个用于GLUT4转运。
