title: Bradykinin potentiates insulin-stimulated glucose uptake and enhances insulin signal through the bradykinin B2 receptor in dog skeletal muscle and rat L6 myoblasts.
abstract: Previously we demonstrated that bradykinin infusion could increase glucose uptake into dog peripheral tissues, and that bradykinin could potentiate insulin-induced glucose uptake through glucose transporter 4 (GLUT4) translocation in dog adipocytes. However, skeletal muscle is the predominant tissue for insulin-mediated glucose disposal. The aim of this study was to determine how bradykinin affected insulin-stimulated glucose uptake in dog skeletal muscle and myotubes transformed from rat L6 myoblasts. The bradykinin receptor binding studies revealed that dog skeletal muscle and rat L6 myoblasts possessed significant numbers of bradykinin receptors (Kd = 88 and 76 pmol/l, Bmax = 82.5 and 20 fmol/mg protein respectively). An RT-PCR (reverse transcriptase-polymerase chain reaction) amplification showed mRNA specific for bradykinin B2 receptor in both cells. Bradykinin significantly increased 2-deoxyglucose uptake in isolated muscle and L6 myoblasts in the presence of insulin (10(-7) mol/l) in a dose-dependent manner, but not in the absence of insulin. Bradykinin also enhanced insulin-stimulated GLUT4 translocation, and insulin-induced phosphorylation of insulin receptor beta subunit and insulin receptor substrate-1 (IRS-1) without affecting the binding affinities or numbers of cell surface insulin receptors in both cells. It is concluded that bradykinin could potentiate the insulin-induced glucose uptake through GLUT4 translocation in dog skeletal muscle and rat L6 myoblasts. This effect could be explained by the potency of bradykinin to upregulate the insulin receptor tyrosine kinase activity which stimulates phosphorylation of IRS-1, followed by an increase in GLUT4 translocation.
authors.affiliation: Department of Metabolic Medicine, Kumamoto University School of Medicine, Honjo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Miyata
authors.forename: T
authors.initials: T
authors.lastname: Taguchi
authors.forename: M
authors.initials: M
authors.lastname: Uehara
authors.forename: S
authors.initials: S
authors.lastname: Isami
authors.forename: H
authors.initials: H
authors.lastname: Kishikawa
authors.forename: K
authors.initials: K
authors.lastname: Kaneko
authors.forename: E
authors.initials: E
authors.lastname: Araki
authors.forename: M
authors.initials: M
authors.lastname: Shichiri
mesh_terms: D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D001667:Binding, Competitive; D001920:Bradykinin / Q000032:analysis / Q000378:metabolism* / Q000494:pharmacology; D002460:Cell Line; D017931:DNA Primers / Q000737:chemistry; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism* / Q000494:pharmacology; D055504:Insulin Receptor Substrate Proteins; D008297:Male; D018482:Muscle, Skeletal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010750:Phosphoproteins / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D051381:Rats; D011972:Receptor, Insulin / Q000187:drug effects / Q000378:metabolism*; D018002:Receptors, Bradykinin / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D014316:Tritium
chemical_list: D017931:DNA Primers; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526296:Irs1 protein, rat; D010750:Phosphoproteins; D012333:RNA, Messenger; D018002:Receptors, Bradykinin; D014316:Tritium; D011972:Receptor, Insulin; D005947:Glucose; D001920:Bradykinin