A Crucial Role for the Small GTPase Rac1 Downstream of the Protein Kinase Akt2 in Insulin Signaling that Regulates Glucose Uptake in Mouse Adipocytes
| Autor: | Sayaka Matsui, Nobuyuki Takenaka, Mika Nakao, Takaya Satoh |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
rac1 GTP-Binding Protein
0301 basic medicine Glucose uptake Chromosomal translocation glut4 lcsh:Chemistry Mice 0302 clinical medicine Adipocytes Small GTPase lcsh:QH301-705.5 Spectroscopy rac1 Glucose Transporter Type 4 biology Chemistry General Medicine RALA Computer Science Applications Cell biology Protein Transport 030220 oncology & carcinogenesis embryonic structures RNA Interference hormones hormone substitutes and hormone antagonists Signal Transduction insulin gtpase adipocyte Article Catalysis akt2 Inorganic Chemistry 03 medical and health sciences 3T3-L1 Cells Animals Physical and Theoretical Chemistry Protein kinase A Molecular Biology Organic Chemistry Glucose transporter glucose uptake Insulin receptor Glucose 030104 developmental biology Microscopy Fluorescence lcsh:Biology (General) lcsh:QD1-999 biology.protein ral GTP-Binding Proteins Proto-Oncogene Proteins c-akt GLUT4 |
| Zdroj: | International Journal of Molecular Sciences, Vol 20, Iss 21, p 5443 (2019) International Journal of Molecular Sciences Volume 20 Issue 21 |
| ISSN: | 1422-0067 |
| Popis: | Insulin-stimulated glucose uptake is mediated by translocation of the glucose transporter GLUT4 to the plasma membrane in adipocytes and skeletal muscle cells. In both types of cells, phosphoinositide 3-kinase and the protein kinase Akt2 have been implicated as critical regulators. In skeletal muscle, the small GTPase Rac1 plays an important role downstream of Akt2 in the regulation of insulin-stimulated glucose uptake. However, the role for Rac1 in adipocytes remains controversial. Here, we show that Rac1 is required for insulin-dependent GLUT4 translocation also in adipocytes. A Rac1-specific inhibitor almost completely suppressed GLUT4 translocation induced by insulin or a constitutively activated mutant of phosphoinositide 3-kinase or Akt2. Constitutively activated Rac1 also enhanced GLUT4 translocation. Insulin-induced, but not constitutively activated Rac1-induced, GLUT4 translocation was abrogated by inhibition of phosphoinositide 3-kinase or Akt2. On the other hand, constitutively activated Akt2 caused Rac1 activation, and insulin-induced Rac1 activation was suppressed by an Akt2-specific inhibitor. Moreover, GLUT4 translocation induced by a constitutively activated mutant of Akt2 or Rac1 was diminished by knockdown of another small GTPase RalA. RalA was activated by a constitutively activated mutant of Akt2 or Rac1, and insulin-induced RalA activation was suppressed by an Akt2- or Rac1-specific inhibitor. Collectively, these results suggest that Rac1 plays an important role in the regulation of insulin-dependent GLUT4 translocation downstream of Akt2, leading to RalA activation in adipocytes. |
| Databáze: | OpenAIRE |
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