The Rho family GTPase Rac1 has been implicated in the regulation of glucose uptake in myoblast cell lines. However, no evidence for the role of Rac1 has been provided by a mouse model. The purpose of this study is to test the involvement of Rac1 in insulin action in mouse skeletal muscle. Intravenous administration of insulin indeed elicited Rac1 activation in gastrocnemius muscle, suggesting the involvement of Rac1 in this signaling pathway. We then examined whether insulin-stimulated translocation of the facilitative glucose transporter GLUT4 from its storage sites to the skeletal muscle sarcolemma depends on Rac1. We show that ectopic expression of constitutively activated Rac1, as well as intravenous administration of insulin, caused translocation of GLUT4 to the gastrocnemius muscle sarcolemma, as revealed by immunofluorescent staining of a transiently expressed exofacial epitope-tagged GLUT4 reporter. Of particular note, insulin-dependent, but not constitutively activated Rac1-induced, GLUT4 translocation was markedly suppressed in skeletal muscle-specific rac1-knockout mice compared to control mice. Immunogold electron microscopic analysis of endogenous GLUT4 gave similar results. Collectively, we propose a critical role of Rac1 in insulin-dependent GLUT4 translocation to the skeletal muscle sarcolemma, which has heretofore been predicted solely by cell culture studies.

TAC is well tolerated and effective when used as an add-on to biological DMARDs in Japanese patients with RA who do not achieve an adequate response to biological DMARDs in a real-world clinical setting.

In this commentary, the authors review one area of federal policy, adult basic education policy, since its inception in the 1960s as an example of how educational policy can drift from its broad purpose as it responds to political, social, and economic forces. The authors argue that its current narrow focus on workforce development underestimates the challenges of improving employment and earnings outcomes. More important, it undercuts the value and benefits of skill gains that can accrue before participants are able to attain jobs that can improve their economic outlook. Analysis of adult skill assessments indicate that even small skill increases can have a significant impact on other important social outcomes. Thus, the authors call for broadening the goal of federal adult basic education programs from primarily workforce development to helping participants more effectively fulfill a range of adult roles and responsibilities.