AJP - Heart Calcium Transients and Cell-Sarcomere
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Am J Physiol Heart Circ Physiol 289: H2478-H2483, 2005. First published August 5, 2005; doi:10.1152/ajpheart.00638.2005
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Depressed cardiac myofilament function in human diabetes mellitus

Eias E. Jweied,1,2,4 Ronald D. McKinney,1,2 Lori A. Walker,1,2,3 Irwin Brodsky,3 Alexander S. Geha,4 Malek G. Massad,4 Peter M. Buttrick,1,2,3 and Pieter P. de Tombe1,2,3

1Center for Cardiovascular Research, 2Department of Physiology and Biophysics, 3Department of Medicine, and 4Division of Cardiothoracic Surgery, Department of Surgery, University of Illinois at Chicago, Chicago, Illinois

Submitted 14 June 2005 ; accepted in final form 1 August 2005

Diabetes mellitus is associated with a distinct cardiomyopathy. Whether cardiac myofilament function is altered in human diabetes mellitus is unknown. Myocardial biopsies were obtained from seven diabetic patients and five control, nondiabetic patients undergoing coronary artery bypass surgery. Myofilament function was assessed by determination of the developed force-Ca2+ concentration relation in skinned cardiac cells from flash-frozen human biopsies. Separate control experiments revealed that flash freezing of biopsy specimens did not affect myofilament function. All patients in the diabetes mellitus cohort were classified as Type 2 diabetes mellitus patients, and most showed signs of diastolic dysfunction. Diabetes mellitus was associated with depressed myofilament function, that is, decreased Ca2+ sensitivity (29%, P < 0.05 vs. control) and a trend toward reduction of maximum Ca2+-saturated force (29%, P = 0.08 vs. control). The slope of the force-Ca2+ concentration relation (Hill coefficient) was not affected by diabetes, however. We conclude that human diabetes mellitus is associated with decreased cardiac myofilament function. Depressed cardiac myofilament Ca2+ responsiveness may underlie the decreased ventricular function characteristic of human diabetic cardiomyopathy.

heart failure; myofilament function; skinned myocardium; sarcomere


Address for reprint requests and other correspondence: P. P. de Tombe, Dept. of Physiology and Biophysics, (M/C 901), College of Medicine, Univ. of Illinois at Chicago, 835 S. Wolcott Ave., Chicago, IL 60612 (e-mail: pdetombe{at}uic.edu)




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