Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
von Lewinski, D; Gasser, R; Rainer, PP; Huber, MS; Wilhelm, B; Roessl, U; Haas, T; Wasler, A; Grimm, M; Bisping, E; Pieske, B.
Functional effects of glucose transporters in human ventricular myocardium.
Eur J Heart Fail. 2010; 12(2):106-113
Doi: 10.1093/eurjhf/hfp191
[OPEN ACCESS]
Web of Science
PubMed
FullText
FullText_MUG
Google Scholar
- Führende Autor*innen der Med Uni Graz
- von Lewinski Dirk
- Co-Autor*innen der Med Uni Graz
- Bisping Egbert Hubertus
- Gasser Robert
- Pieske Burkert Mathias
- Rainer Peter
- Rössl Ulrich
- Wasler Andrae
- Altmetrics:
- Dimensions Citations:
- Plum Analytics:
- Scite (citation analytics):
- Abstract:
- 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). 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. 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.
- Find related publications in this database (using NLM MeSH Indexing)
- Aged -
- Carbonates - pharmacology
- Cardiomyopathy, Dilated - physiopathology
- Dose-Response Relationship, Drug -
- Female -
- Gene Expression Regulation -
- Glucose Transporter Type 1 - genetics Glucose Transporter Type 1 - metabolism
- Glucose Transporter Type 4 - genetics Glucose Transporter Type 4 - metabolism
- Glucosides - pharmacology
- Heart Failure - physiopathology
- Heart Ventricles -
- Humans -
- Inhibitory Concentration 50 -
- Insulin - pharmacology
- Male -
- Middle Aged -
- Myocardial Contraction - drug effects Myocardial Contraction - physiology
- Myocardial Ischemia - physiopathology
- Myocardium - metabolism
- Phosphatidylinositol 3-Kinases - antagonists and inhibitors
- RNA, Messenger - metabolism
- Sodium-Glucose Transporter 1 - antagonists and inhibitors Sodium-Glucose Transporter 1 - genetics Sodium-Glucose Transporter 1 - metabolism
- Sodium-Glucose Transporter 2 - antagonists and inhibitors Sodium-Glucose Transporter 2 - genetics Sodium-Glucose Transporter 2 - metabolism
- Find related publications in this database (Keywords)
- Insulin
- Glucose transport
- Heart failure
- Human myocardium