GLUT4 ablation in mice results in redistribution of IRAP to the plasma membrane

Glucose transporter (GLUT) 4 is the insulin responsive glucose transporter in adipose tissue, skeletal muscle, and heart. insulin elicits increased gl ucose uptake by recruiting GLUT4 from a specialized intracellular storage s ite to the cell surface. Expression of various proteins that colocalize wit h GLUT4 and/or are involved in insulin-stimulated GLUT4 translocation was e xamined in adipocytes as well as skeletal and cardiac muscles from GLUT4 nu ll mice. Our data demonstrate that expression of insulin-regulated ami nope ptidase (IRAP) is divergently regulated in GLUT4 null tissues, e.g., upregu lated Id-fold in GLUT4 null adipocytes and downregulated in GLUT4 null skel etal muscle (40%) and heart (60%). IRAP exhibited abnormal subcellular dist ribution and impaired insulin-stimulated translocation in GLUT4-deficient t issues. We propose the compartment containing IRAP and proteins normally as sociated with GLUT4 vesicle traffics constitutively to the cell surface in GLUT4 null adipocytes and skeletal muscle. (C) 2001 Academic Press.