Document Detail


Glucose-transporter-mediated positive inotropic effects in human myocardium of diabetic and nondiabetic patients.
MedLine Citation:
PMID:  20045149     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Insulin causes inotropic effects via Ca(2+)-dependent and Ca(2+)-independent pathways. The latter one is potentially glucose dependent. We examined inotropic responses and signal transduction of insulin in human atrial myocardium of diabetic and nondiabetic patients to test for the role of glucose transporters. Experiments were performed in isolated atrial myocardium of 88 patients undergoing cardiac surgery and 28 ventricular muscle samples of explanted hearts. Influence of insulin (0.02 micromol/L) on isometric twitch force was examined with and without blocking glucose transporter (GLUT) 4 translocation (latrunculin), sodium-coupled glucose transporter (SGLT) 1 (phlorizin, T-1095A), or PI3-kinase (wortmannin). Experiments were performed in Tyrode solution containing glucose or pyruvate as energetic substrate. Messenger RNA expression of glucose transporters (GLUT1, GLUT4, SGLT1, SGLT2) was analyzed in atrial and ventricular myocardium of both diabetic and nondiabetic patients. Developed force increases after insulin (to 117.8% +/- 2.4% and 115.8% +/- 1.9%) in trabeculae from patients with and without diabetes. Inotropic effect was reduced after displacing glucose with pyruvate as well as after PI3-kinase inhibition (to 103% +/- 2%) or inhibition of glucose transporters GLUT4 (to 105% +/- 2%) and SGLT1 (phlorizin to 106% +/- 2%, T-1095A to 105% +/- 2%), without differences between the 2 groups. In glucose-free pyruvate-containing solution, only inhibition of PI3-kinase but not blocking glucose transporters resulted in further inhibitory effects. Messenger RNA expression did not show significant differences between patients with or without diabetes. Insulin exerts positive inotropic effects in human atrial myocardium. These effects are mediated via a PI3-kinase-sensitive and a glucose-transport-sensitive pathway. Differences in functional effects or messenger RNA expression of glucose transporters were not detectable between patients with and without diabetes.
Authors:
Dirk von Lewinski; Peter P Rainer; Robert Gasser; Marie-Sophie Huber; Mounir Khafaga; Bastian Wilhelm; Tobias Haas; Heinrich M?chler; Ulrich R?ssl; Burkert Pieske
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-12-31
Journal Detail:
Title:  Metabolism: clinical and experimental     Volume:  59     ISSN:  1532-8600     ISO Abbreviation:  Metab. Clin. Exp.     Publication Date:  2010 Jul 
Date Detail:
Created Date:  2010-06-07     Completed Date:  2010-06-17     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0375267     Medline TA:  Metabolism     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1020-8     Citation Subset:  IM    
Affiliation:
Department of Cardiology, Medical University Graz, Graz, Austria. dirk.von-lewinski@medunigraz.at
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MeSH Terms
Descriptor/Qualifier:
1-Phosphatidylinositol 3-Kinase / metabolism
Aged
Cardiotonic Agents / pharmacology
Diabetes Mellitus / metabolism,  physiopathology*
Female
Glucose / metabolism
Glucose Transport Proteins, Facilitative / biosynthesis,  genetics,  physiology*
Heart Atria
Humans
Hypoglycemic Agents / pharmacology
Insulin / pharmacology
Male
Middle Aged
Myocardial Contraction / physiology*
Myocardium / cytology,  metabolism
Pyruvic Acid / metabolism
RNA, Messenger / biosynthesis,  genetics
Sodium-Glucose Transporter 1 / biosynthesis,  genetics
Chemical
Reg. No./Substance:
0/Cardiotonic Agents; 0/Glucose Transport Proteins, Facilitative; 0/Hypoglycemic Agents; 0/RNA, Messenger; 0/Sodium-Glucose Transporter 1; 11061-68-0/Insulin; 127-17-3/Pyruvic Acid; 50-99-7/Glucose; EC 2.7.1.137/1-Phosphatidylinositol 3-Kinase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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