BRADYKININ DIRECTLY TRIGGERS GLUT4 TRANSLOCATION VIA AN INSULIN-INDEPENDENT PATHWAY

Physical exercise induces translocation of GLUT4 from an intracellular pool to the cell surface in skeletal muscles and increases glucose up take via an insulin-independent pathway. However, the molecular mechan ism remains to be identified. Some studies have suggested that bradyki nin is locally released from contracting muscles and may be responsibl e for GLUT4 translocation and the increase of glucose transport in ske letal muscles. To determine whether bradykinin directly triggers GLUT4 translocation, we established L6 myotubes, 3T3-L1 adipocytes, and Chi nese hamster ovary cells stably expressing c-myc epitope-tagged GLUT4 (GLUT4myc) and bradykinin B-2 receptors. We found that bradykinin dire ctly triggered GLUT4myc translocation and increased the rate of glucos e uptake in a dose-dependent manner in these cells. The translocation with bradykinin occurred even after pretreatment with an islet-activat ing protein, wortmannin, and phorbol 12,13-dibutyrate. The signaling p athway does not seem to be mediated by G(i), phosphatidylinositol 3-ki nase, or protein kinase C. It is insulin-independent and via trimeric G-protein G(q). Bradykinin is probably one of the factors responsible for exercise-stimulated glucose uptake in skeletal muscles.