Glucose is fundamental to the metabolism of mammalian cells. Its passage across cell membranes is mediated by a family of transporters termed glucose transporters or Gluts. In adipose and muscle tissue, insulin stimulates a rapid and dramatic increase in glucose uptake, which is largely due to the redistribution of the insulin-inducible glucose transporter, Glut4. In response to insulin, Glut4 is quickly shuttled from an intracellular storage site to the plasma membrane, where it binds glucose. In contrast, the ubiquitously expressed glucose transporter Glut1 is constitutively targeted to the plasma membrane, and shows a much less dramatic translocation in response to insulin. Glut1 and Glut4 are twelve-pass transmembrane proteins (12TM) whose carboxy-termini may dictate their cellular localization. Aberrant Glut4 expression has been suggested to contribute to such maladies as obesity and diabetes. Glut4 null mice have shown that while functional Glut4 protein is not required for maintaining normal glucose levels, it is necessary for sustained growth, normal cellular glucose, fat metabolism and prolonged longevity.