A Role for the CHC22 Clathrin Heavy-Chain Isoform in Human Glucose Metabolism

In human muscle, the GLUT4 glucose transport pathway responds to insulin and is responsible for 70 to 90% of human glucose clearance. In the basal metabolic state, GLUT4 is sequestered away from the cell surface and is released from an intracellular membrane compartment in response to insulin. This GLUT4 membrane pathway is defective in type II diabetes. Vassilopoulos et al. (p. [1192][1]; see the Perspective by Orme and Bogan ) now describe a function for CHC22 clathrin, a second isoform of clathrin that is present in humans and not in mice. CHC22 participates in the biogenesis of the intracellular compartment that sequesters the GLUT4 glucose transporter for insulin-stimulated release. Because CHC22 is restricted to humans, mice differ in their pathways that control glucose metabolism, which may restrict the utility of the mouse as a model system in assessing glucose metabolism and diabetes. [1]: /lookup/doi/10.1126/science.1171529