Glucose transporters and insulin action: Some insights into diabetes management

Insulin stimulates glucose uptake in muscle and adipose cells primarily by recruiting GLUT4 from an intracellular storage pool to the plasma membrane. Dysfunction of this process known as insulin resistance causes hyperglycem ia, a hallmark of diabetes and obesity. Thus the understanding of the mecha nisms underlying this process at the molecular level may give an insight in to the prevention and treatment of these health problems. GLUT4 in rat adip ocytes, for example, constantly recycles between the cell surface and an in tracellular pool by endocytosis and exocytosis, each of which is regulated by an insulin-sensitive and GLUT4-selective sorting mechanism. Our working hypothesis has been that this sorting mechanism includes a specific interac tion of a cytosolic protein with the GLUT4 cytoplasmic domain. Indeed, a sy nthetic peptide of the C-terminal cytoplasmic domain of GLUT4 induces an in sulin-like GLUT4 recruitment when introduced in rat adipocytes. Relevance o f these observations to a novel euglycemic drug design is discussed.