| Functional effects of glucose transporters in human ventricular myocardium. | |
| | |
MedLine Citation:
|
PMID: 20083620 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
AIMS: 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). METHODS AND 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:
|
Dirk von Lewinski; Robert Gasser; Peter P Rainer; Marie-Sophie Huber; Bastian Wilhelm; Ulrich Roessl; Tobias Haas; Andrae Wasler; Michael Grimm; Egbert Bisping; Burkert Pieske |
Publication Detail:
|
Type: In Vitro; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
|
Title: European journal of heart failure Volume: 12 ISSN: 1879-0844 ISO Abbreviation: Eur. J. Heart Fail. Publication Date: 2010 Feb |
Date Detail:
|
Created Date: 2010-01-19 Completed Date: 2011-01-20 Revised Date: 2011-06-08 |
Medline Journal Info:
|
Nlm Unique ID: 100887595 Medline TA: Eur J Heart Fail Country: Netherlands |
Other Details:
|
Languages: eng Pagination: 106-13 Citation Subset: IM |
Affiliation:
|
Department of Cardiology, Working Group Metabolism and Energetics, Medical University Graz, Graz, Austria. dirk.von-lewinski@medunigraz.at |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Aged Carbonates / pharmacology Cardiomyopathy, Dilated / physiopathology Dose-Response Relationship, Drug Female Gene Expression Regulation Glucose Transporter Type 1 / genetics, metabolism* Glucose Transporter Type 4 / genetics, metabolism* Glucosides / pharmacology Heart Failure / physiopathology* Heart Ventricles Humans Inhibitory Concentration 50 Insulin / pharmacology Male Middle Aged Myocardial Contraction / drug effects, physiology* Myocardial Ischemia / physiopathology Myocardium / metabolism* Phosphatidylinositol 3-Kinases / antagonists & inhibitors RNA, Messenger / metabolism Sodium-Glucose Transporter 1 / antagonists & inhibitors, genetics, metabolism* Sodium-Glucose Transporter 2 / antagonists & inhibitors, genetics, metabolism |
| Chemical | |
Reg. No./Substance:
|
0/Carbonates; 0/Glucose Transporter Type 1; 0/Glucose Transporter Type 4; 0/Glucosides; 0/RNA, Messenger; 0/Sodium-Glucose Transporter 1; 0/Sodium-Glucose Transporter 2; 0/T 1095; 11061-68-0/Insulin; EC 2.7.1.-/Phosphatidylinositol 3-Kinases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Ageing and gait variability--a population-based study of older people.
Next Document: Prevalence and natural history of heart disease in adults with primary mitochondrial respiratory cha...