TC10alpha is required for insulin-stimulated glucose uptake in adipocytes.
Previous studies have suggested that activation of the Rho family member GTPase TC10 is necessary but not sufficient for the stimulation of glucose transport by insulin. We show here that endogenous TC10alpha is rapidly activated in response to insulin in 3T3L1 adipocytes in a phosphatidylinositol 3-kinase-independent manner, whereas platelet-derived growth factor was without effect. Knockdown of TC10alpha but not TC10beta by RNA interference inhibited insulin-stimulated glucose uptake as well as the translocation of the insulin-sensitive glucose transporter GLUT4 from intracellular sites to the plasma membrane. In contrast, loss of TC10alpha had no effect on the stimulation of Akt by insulin. Additionally, knockdown of TC10alpha inhibited insulin-stimulated translocation of its effector CIP4. These data indicate that TC10alpha is specifically required for insulin-stimulated glucose uptake in adipocytes.
Chang
Louise
L
Life Sciences Institute, University of Michigan Medical Center, Ann Arbor, Michigan 48109-2216, USA.
Chiang
Shian-Huey
SH
Saltiel
Alan R
AR
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D005947:Glucose / Q000493:pharmacokinetics*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology*; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D015778:Minor Histocompatibility Antigens; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034741:RNA, Small Interfering; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D020741:rho GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
D007004:Hypoglycemic Agents; D007328:Insulin; D008869:Microtubule-Associated Proteins; D015778:Minor Histocompatibility Antigens; D034741:RNA, Small Interfering; C485787:Trip10 protein, mouse; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; C503260:Rhoq protein, mouse; D020741:rho GTP-Binding Proteins; D005947:Glucose