ALAN SALTIEL

..Thus, there are two isoforms of this key signaling intermediate, both of which are activated by insulin, but they may play different roles in initiating downstream effectors that influence glucose transport...

..But recent studies have shown that numerous other hormones and signalling events attenuate insulin action, and are important in type 2 diabetes...

..These events play crucial roles in the trafficking, docking and fusion of vesicles containing the insulin-responsive glucose transporter Glut4 at the plasma membrane...

..Also, the rapid termination of tyrosine or lipid phosphorylation by phosphatases or serine kinases might tightly control the strength of a signaling pathway, thus determining its effect on growth, differentiation and metabolism...

..Thus, both c-Cbl and Cbl-b can initiate a phosphatidylinositol 3-kinase/protein kinase B-independent signaling pathway critical to insulin-stimulated GLUT4 translocation...

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..Thus, TCGAP may act as a downstream effector of TC10 in the regulation of insulin-stimulated glucose transport...

..So, the exocyst might have a crucial role in the targeting of the Glut4 vesicle to the plasma membrane, perhaps directing the vesicle to the precise site of fusion...

..This suggests that insulin/insulin-like growth factor signaling pathways not only prevent the induction of autophagy, but paradoxically may promote autophagy of deleterious proteins in certain circumstances...

..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...

..These pathways converge to control the recycling of the facilitative glucose transporter Glut4...

..These data suggest that CIP4/2 may play an important role in insulin-stimulated glucose transport as a downstream effector of TC10...

..We describe experimental approaches using the insulin-responsive cell line 3T3-L1 adipocytes to study the role of TC10 in insulin-stimulated glucose transport...

..These results suggest that the TC10/exocyst complex/SAP97 axis plays an important role in the tethering of Glut4 vesicles to the plasma membrane in adipocytes...

..These data suggest that PTG plays a critical role in glycogen synthesis and is necessary to maintain the appropriate metabolic balance for the partitioning of fuel substrates between glycogen and lipid...

..Thus, TORC2 might serve as a gluconeogenic "molecular switch" that senses hormones and cellular energy status...

..Taken together, these data indicate that the insulin receptor directly catalyzes the tyrosine phosphorylation of caveolin...

..Together, these studies suggest that the TC10/GAPEX-5/Rab5 axis mediates insulin-stimulated production of PI(3)P, which regulates trafficking of Glut4 vesicles...

..Our results provide a framework to investigate how additional transcription factors may regulate PTG expression in other cell types...

..Thus, RalA serves two functions in insulin action: as a cargo receptor for the Myo1c motor, and as a signal for the unification of the exocyst to target Glut4 vesicles to the plasma membrane...

..Thus both indirect/secreted and direct/cell contact-mediated factors derived from macrophages influence insulin sensitivity in adipocytes...

..Insulin recruits the CIP4/Gapex-5 complex to the plasma membrane, thus reducing Rab31 activity and permitting Glut4 vesicles to translocate to the cell surface, where Glut4 docks and fuses to transport glucose into the cell...

..Thus, diet-induced obesity leads to a shift in the activation state of ATMs from an M2-polarized state in lean animals that may protect adipocytes from inflammation to an M1 proinflammatory state that contributes to insulin resistance...

..These findings demonstrate a role for integrin alpha6 in connecting morphogenesis with signaling processes leading to terminal differentiation...

..Thus, IKKepsilon may represent an attractive therapeutic target for obesity, insulin resistance, diabetes, and other complications associated with these disorders...

..Both in vivo and in vitro studies indicate their role in regulating whole-body energy metabolism, and possibly weight gain as well. The promise and challenges presented by this new class of drug discovery targets will also be discussed...

..Down-regulation of GAPex-5 impaired insulin-stimulated PKB/Akt activation. Collectively, this study indicates the involvement of Rab5 in insulin signaling...

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..Together, these data demonstrate that TC10 can differentially regulate two types of filamentous actin in adipocytes dependent on distinct functional domains and its subcellular compartmentalization...

..Moreover, the transport through the secretory pathway is necessary for the localization of TC10 to lipid raft microdomains at the plasma membrane...

..This structure provides a molecular visualization of one of the initial downstream recruitment events following insulin activation of its dimeric receptor...

..These results have important implications for the design of tailored myocardial protection and operative strategies for diabetic patients undergoing CPB/C...

..We propose that an EGF-stimulated GAP accelerates GTP hydrolysis of TC10, thereby promoting vesicle fusion...

..However, the hormone reduces liver lipids when acutely elevated. Work in this issue of Cell Metabolism (Najjar at al., 2005) suggests a new mechanism for the inhibition of the rate-limiting enzyme in liver, fatty acid synthase...

..We anticipate that these data will present a clearer picture of the regulation of Glut4 trafficking, docking and fusion. ..

..Together, these approaches will allow for the evaluation of the importance of this novel pathway in insulin action, setting the stage for future investigations into its potential role in the development of diabetes. ..

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..Together, these approaches will allow for the evaluation of the importance of this novel pathway in insulin action, setting the stage for future investigations into its potential role in the development of diabetes. ..

..We anticipate that these data will present a clearer picture of the regulation of Glut4 trafficking, docking and fusion. ..

..Together, these approaches will allow for the evaluation of the importance of this novel pathway in insulin action, setting the stage for future investigations into its potential role in the development of diabetes. ..

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..Together, these approaches will allow for the evaluation of the importance of this novel pathway in insulin action, setting the stage for future investigations into its potential role in the development of diabetes. ..

..Together, these approaches will allow for the evaluation of the importance of this pathway in insulin action, setting the stage for future investigations into its potential role in the development of diabetes. ..

..Together, these approaches will allow for the evaluation of the importance of this novel pathway in insulin action, setting the stage for future investigations into its potential role in the development of diabetes. ..

..Together, these approaches will allow for the evaluation of the importance of this novel pathway in insulin action, setting the stage for future investigations into its potential role in the development of diabetes. ..