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 uptake via an insulin-independent pathway. However, the molecular mechanism remains to be identified. Some studies have suggested that bradykinin is locally released from contracting muscles and may be responsible for GLUT4 translocation and the increase of glucose transport in skeletal muscles. To determine whether bradykinin directly triggers GLUT4 translocation, we established L6 myotubes, 3T3-L1 adipocytes, and Chinese hamster ovary cells stably expressing c-myc epitope-tagged GLUT4 (GLUT4myc) and bradykinin B2 receptors. We found that bradykinin directly triggered GLUT4myc translocation and increased the rate of glucose uptake in a dose-dependent manner in these cells. The translocation with bradykinin occurred even after pretreatment with an islet-activating protein, wortmannin, and phorbol 12,13-dibutyrate. The signaling pathway does not seem to be mediated by Gi, phosphatidylinositol 3-kinase, or protein kinase C. It is insulin-independent and via trimeric G-protein Gq. Bradykinin is probably one of the factors responsible for exercise-stimulated glucose uptake in skeletal muscles.
Kishi
K
K
Division of Molecular Genetics, Institute for Enzyme Research, The University of Tokushima, Japan.
Muromoto
N
N
Nakaya
Y
Y
Miyata
I
I
Hagi
A
A
Hayashi
H
H
Ebina
Y
Y
D016475:3T3 Cells; D017667:Adipocytes / Q000378:metabolism; D000818:Animals; D001692:Biological Transport; D001920:Bradykinin / Q000502:physiology*; D016466:CHO Cells; D006224:Cricetinae; D019204:GTP-Binding Proteins / Q000502:physiology; D015870:Gene Expression; D016259:Genes, myc; D005947:Glucose / Q000378:metabolism; D051275:Glucose Transporter Type 4; D006003:Glycogen / Q000096:biosynthesis; D006801:Humans; D007328:Insulin / Q000502:physiology*; D007739:L Cells; D051379:Mice; D009004:Monosaccharide Transport Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D009124:Muscle Proteins; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000648:ultrastructure; D011493:Protein Kinase C / Q000502:physiology; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin / Q000378:metabolism
D051275:Glucose Transporter Type 4; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin; C495692:SLC2A4 protein, human; C495693:Slc2a4 protein, mouse; D006003:Glycogen; D011493:Protein Kinase C; D019204:GTP-Binding Proteins; D005947:Glucose; D001920:Bradykinin