Muscling in on GLUT4 kinetics

Insulin triggers glucose uptake into muscle and adipose tissue by stimulating the translocation of the glucose transporter GLUT4 from intracellular vesicles to the plasma membrane (PM). Insulin leads to a rapid increase in GLUT4 at the PM from ~5% to 40-50%. This effect is time and dose-dependent, reaching a new steady state after 30 min of insulin stimulation. Previous kinetic analyses in adipocytes has revealed that this is regulated by two mechanisms – increasing the amount of GLUT4 in the endosomal recycling system and increasing the exocytosis rate constant. Fazakerley et al1 focuses on GLUT4 kinetics in the L6 skeletal muscle cell line. Despite displaying a similar redistribution of GLUT4 to the cell surface with insulin to that seen in adipocytes, the mechanism for this effect in L6 cells was completely different. Insulin had a modest effect to increase the amount of GLUT4 in the recycling system with the dominant effect being on reduction of the endocytosis rate constant. Similar findings were observed with AMPK agonists. These studies indicate that different cell types are capable of achieving the same cell biological endpoint but using completely distinct mechanisms.