title: Functional effects of glucose transporters in human ventricular myocardium.
abstract: OBJECTIVE
  Insulin-dependent positive inotropic effects (PIE) are partially Ca(2+) independent. This mechanism is potentially glucose dependent. In contrast to most animal species, human myocardium expresses high levels of sodium-glucose-transporter-1 (SGLT-1) mRNA besides the common glucose-transporters-1 and -4 (GLUT1, GLUT4).
  
  
  RESULTS
  We used ventricular myocardium from 61 end-stage failing human hearts (ischaemic cardiomyopathy, ICM and dilated cardiomyopathy, DCM) and 13 non-failing donor hearts. The effect of insulin on isometric twitch force was examined with or without blocking of PI3-kinase, GLUT4-translocation, or SGLT-1. Substrate-dependent (glucose vs. pyruvate vs. palmitoyl-carnitine) effects were tested in atrial myocardium. mRNA expression of glucose transporters was analysed. Insulin increased developed force by 122 + or - 7.4, 121.7 + or - 2.5, and 134.1 + or - 5.7% in non-failing, DCM, and ICM (P < 0.05 vs. DCM), respectively. Positive inotropic effect was partially blunted by inhibition of PI-3-kinase, GLUT4, or SGLT1. Combined inhibition of PI3-kinase and glucose-transport completely abolished PIE. Positive inotropic effect was significantly stronger in glucose-containing solution compared with pyruvate or palmitoyl-carnitine containing. mRNA expression showed only a tendency towards elevated GLUT4-expression in ICM.
  
  
  CONCLUSIONS
  Positive inotropic effect of insulin is pronounced in ICM, but underlying mechanisms are unaltered. The Ca(2+)-independent PIE of insulin is mediated via glucose-transporters. Together with the Ca(2+)-dependent PI-3-kinase mediated pathway, it is responsible for the entire PIE. Substrate-dependency affirms a glucose-dependent part of the PIE.
authors.affiliation: Department of Cardiology, Working Group Metabolism and Energetics, Medical University Graz, Graz, Austria. dirk.von-lewinski@medunigraz.at
authors.forename: Dirk
authors.initials: D
authors.lastname: von Lewinski
authors.forename: Robert
authors.initials: R
authors.lastname: Gasser
authors.forename: Peter P
authors.initials: PP
authors.lastname: Rainer
authors.forename: Marie-Sophie
authors.initials: MS
authors.lastname: Huber
authors.forename: Bastian
authors.initials: B
authors.lastname: Wilhelm
authors.forename: Ulrich
authors.initials: U
authors.lastname: Roessl
authors.forename: Tobias
authors.initials: T
authors.lastname: Haas
authors.forename: Andrae
authors.initials: A
authors.lastname: Wasler
authors.forename: Michael
authors.initials: M
authors.lastname: Grimm
authors.forename: Egbert
authors.initials: E
authors.lastname: Bisping
authors.forename: Burkert
authors.initials: B
authors.lastname: Pieske
mesh_terms: D000368:Aged; D002254:Carbonates / Q000494:pharmacology; D002311:Cardiomyopathy, Dilated / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D005260:Female; D005786:Gene Expression Regulation; D051272:Glucose Transporter Type 1 / Q000235:genetics / Q000378:metabolism*; D051275:Glucose Transporter Type 4 / Q000235:genetics / Q000378:metabolism*; D005960:Glucosides / Q000494:pharmacology; D006333:Heart Failure / Q000503:physiopathology*; D006352:Heart Ventricles; D006801:Humans; D066298:In Vitro Techniques; D020128:Inhibitory Concentration 50; D007328:Insulin / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology*; D017202:Myocardial Ischemia / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D012333:RNA, Messenger / Q000378:metabolism; D051269:Sodium-Glucose Transporter 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051297:Sodium-Glucose Transporter 2 / Q000235:genetics / Q000378:metabolism; D000077203:Sodium-Glucose Transporter 2 Inhibitors
chemical_list: D002254:Carbonates; D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D005960:Glucosides; D007328:Insulin; D000081082:Phosphoinositide-3 Kinase Inhibitors; D012333:RNA, Messenger; D051269:Sodium-Glucose Transporter 1; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors; C121396:T 1095