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Insulin And Non-Insulin Dependent Glut4 Trafficking: Regulation By The Tug Protein, Stephen Devries

Yale Medicine Thesis Digital Library

The body tightly regulates glucose production and disposal despite changing metabolic demands, including large post-prandial and fasting fluctuations. Specifically, under the action of insulin, muscle contraction, ischemia, and poor nutrient availability, cells increase the amount of the glucose transporter type 4 (GLUT4) at the plasma membrane by mobilizing a sequestered pool of transporters. In this work, we demonstrate that the TUG (tether containing a UBX domain for GLUT4) protein mediates both insulin-dependent and insulin-independent pathways to increase GLUT4 at the plasma membrane. In mice fed a high fat diet to induce insulin resistance, the regulation of the endoproteolytic cleavage of …