title: Role of kallikrein-kininogen system in insulin-stimulated glucose transport after muscle contractions.
abstract: Serum proteins [molecular weight (MW) > 10,000] are essential for increased insulin-stimulated glucose transport after in vitro muscle contractions. We investigated the role of the kallikrein-kininogen system, including bradykinin, which is derived from kallikrein (MW > 10,000)-catalyzed degradation of serum protein kininogen (MW > 10,000), on this contraction effect. In vitro electrical stimulation of rat epitrochlearis muscles was performed in 1) rat serum +/- kallikrein inhibitors; 2) human plasma (normal or kallikrein-deficient); 3) rat serum +/- bradykinin receptor-2 inhibitors; or 4) serum-free buffer +/- bradykinin. 3-O-methylglucose transport (3-MGT) was measured 3.5 h later. Serum +/- kallikrein inhibitors tended (P = 0.08) to diminish postcontraction insulin-stimulated 3-MGT. Contractions in normal plasma enhanced insulin-stimulated 3-MGT vs. controls, but contractions in kallikrein-deficient plasma did not. Supplementing rat serum with bradykinin receptor antagonist HOE-140 during contraction did not alter insulin-stimulated 3-MGT. Muscles stimulated to contract in serum-free buffer plus bradykinin did not have enhanced insulin-stimulated 3-MGT. Bradykinin was insufficient for postcontraction-enhanced insulin sensitivity. However, results with kallikrein inhibitors and kallikrein-deficient plasma suggest kallikrein plays a role in this improved insulin action.
authors.affiliation: Biodynamics Laboratory, Department of Kinesiology, University of Wisconsin, Madison, Wisconsin 53706, USA. dumkecl@appstate.edu
authors.forename: C L
authors.initials: CL
authors.lastname: Dumke
authors.forename: J
authors.initials: J
authors.lastname: Kim
authors.forename: E B
authors.initials: EB
authors.lastname: Arias
authors.forename: G D
authors.initials: GD
authors.lastname: Cartee
mesh_terms: D019325:3-O-Methylglucose / Q000378:metabolism*; D000218:Adamantane / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D007611:Aprotinin / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D001790:Blood Physiological Phenomena; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000494:pharmacology; D065168:Bradykinin Receptor Antagonists; D004338:Drug Combinations; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D007610:Kallikreins / Q000037:antagonists & inhibitors / Q000502:physiology*; D007704:Kininogens / Q000502:physiology*; D008297:Male; D009119:Muscle Contraction / Q000502:physiology*; D010940:Plant Proteins / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D043782:Receptor, Bradykinin B2; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology; D014325:Tromethamine / Q000494:pharmacology; D014361:Trypsin Inhibitors
chemical_list: D065168:Bradykinin Receptor Antagonists; D004338:Drug Combinations; D007328:Insulin; D007704:Kininogens; C074097:Krebs-Henseleit solution; D010940:Plant Proteins; D043782:Receptor, Bradykinin B2; D015842:Serine Proteinase Inhibitors; D014361:Trypsin Inhibitors; D014325:Tromethamine; C074544:bradykinin, 1-adamantanecarboxylic acid-Arg(0)-Hyp(3)-Thi(5,8)-Phe(7)-; D019325:3-O-Methylglucose; C065679:icatibant; C069599:trypsin inhibitor protein, Brassica napus; D007611:Aprotinin; D007610:Kallikreins; D005947:Glucose; D000218:Adamantane; D001920:Bradykinin