© 1999 by European Society of Cardiology
Copyright © 1999, European Society of Cardiology
Insulin resistance in patients with cardiac hypertrophy1
aMRC Cyclotron Unit, Imperial College School of Medicine, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK
bQueen Elizabeth Hospital, Birmingham, UK
* Corresponding author. Tel.: +44-181-383-3186; fax: +44-181-383-3742. E-mail address: paolo@cu.rpms.ac.uk (P.G. Camici)
Objective: Animal studies suggest that left ventricular hypertrophy might be associated with insulin resistance and alterations in glucose transporters. We have previously demonstrated myocardial insulin resistance in patients with post-ischemic heart failure. The aim was to investigate whether myocardial insulin resistance could be demonstrated in human cardiac hypertrophy in the absence of hypertension, diabetes and coronary artery disease. Methods: Eleven normotensive nondiabetic patients with cardiac hypertrophy due to aortic stenosis and angiographically normal coronary arteries were compared to 11 normal volunteers. Myocardial glucose uptake (MGU) was measured with positron emission tomography and [18F]2-fluoro-2-deoxy-D-glucose during fasting (low insulinemia) or during euglycemic–hyperinsulinemic clamp (physiologic hyperinsulinemia). Myocardial biopsies were obtained in order to investigate changes in insulin-independent (GLUT-1) and insulin-dependent (GLUT-4) glucose transporters. Results: During fasting, plasma insulin (7±1 vs. 6±1 mU/l) and MGU (0.12±0.05 vs. 0.11±0.04 µmol/min/g) were comparable in patients and controls. By contrast, during clamp, MGU was markedly reduced in patients (0.48±0.02 vs. 0.70±0.03 µmol/min/g, p<0.01) despite similar plasma insulin levels (95±6 vs. 79±6 mU/l). A decreased GLUT-4/GLUT-1 ratio was shown by Western blot analysis in patients. Conclusions: Insulin resistance seems to be a feature of the hypertrophied heart even in the absence of hypertension, coronary artery disease and diabetes and may be explained, at least in part, by abnormalities in glucose transporters.
KEYWORDS Glycolysis; Heart failure; Hyertrophy; Membrane transport; Valve (disease); Positron emission tomography
![]()
CiteULike
Connotea
Del.icio.us What's this?
This article has been cited by other articles:
![]() |
F. Princen, E. Bard, F. Sheikh, S. S. Zhang, J. Wang, W. M. Zago, D. Wu, R. D. Trelles, B. Bailly-Maitre, C. R. Kahn, et al. Deletion of Shp2 Tyrosine Phosphatase in Muscle Leads to Dilated Cardiomyopathy, Insulin Resistance, and Premature Death Mol. Cell. Biol., January 15, 2009; 29(2): 378 - 388. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. C. Villa-Abrille, A. Sidor, and B. O'Rourke Insulin Effects on Cardiac Na+/Ca2+ Exchanger Activity: ROLE OF THE CYTOPLASMIC REGULATORY LOOP J. Biol. Chem., June 13, 2008; 283(24): 16505 - 16513. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. Montessuit, I. Papageorgiou, and R. Lerch Nuclear Receptor Agonists Improve Insulin Responsiveness in Cultured Cardiomyocytes through Enhanced Signaling and Preserved Cytoskeletal Architecture Endocrinology, March 1, 2008; 149(3): 1064 - 1074. [Abstract] [Full Text] [PDF] |
||||
![]() |
Y. G. Ni, N. Wang, D. J. Cao, N. Sachan, D. J. Morris, R. D. Gerard, M. Kuro-o, B. A. Rothermel, and J. A. Hill FoxO transcription factors activate Akt and attenuate insulin signaling in heart by inhibiting protein phosphatases PNAS, December 18, 2007; 104(51): 20517 - 20522. [Abstract] [Full Text] [PDF] |
||||
![]() |
J.-Y. Deng, J.-P. Huang, L.-S. Lu, and L.-M. Hung Impairment of cardiac insulin signaling and myocardial contractile performance in high-cholesterol/fructose-fed rats Am J Physiol Heart Circ Physiol, August 1, 2007; 293(2): H978 - H987. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. P. Dutka, M. Pitt, D. Pagano, M. Mongillo, D. Gathercole, R. S. Bonser, and P. G. Camici Myocardial Glucose Transport and Utilization in Patients With Type 2 Diabetes Mellitus, Left Ventricular Dysfunction, and Coronary Artery Disease J. Am. Coll. Cardiol., December 5, 2006; 48(11): 2225 - 2231. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. J. Murray, C. A. Lygate, M. A. Cole, C. A. Carr, G. K. Radda, S. Neubauer, and K. Clarke Insulin resistance, abnormal energy metabolism and increased ischemic damage in the chronically infarcted rat heart Cardiovasc Res, July 1, 2006; 71(1): 149 - 157. [Abstract] [Full Text] [PDF] |
||||
![]() |
I. Thiele, N. D. Price, T. D. Vo, and B. O. Palsson Candidate Metabolic Network States in Human Mitochondria: IMPACT OF DIABETES, ISCHEMIA, AND DIET J. Biol. Chem., March 25, 2005; 280(12): 11683 - 11695. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. Montessuit, N. Rosenblatt-Velin, I. Papageorgiou, L. Campos, C. Pellieux, T. Palma, and R. Lerch Regulation of glucose transporter expression in cardiac myocytes: p38 MAPK is a strong inducer of GLUT4 Cardiovasc Res, October 1, 2004; 64(1): 94 - 104. [Abstract] [Full Text] [PDF] |
||||
![]() |
Z. Y. Fang, J. B. Prins, and T. H. Marwick Diabetic Cardiomyopathy: Evidence, Mechanisms, and Therapeutic Implications Endocr. Rev., August 1, 2004; 25(4): 543 - 567. [Abstract] [Full Text] [PDF] |
||||
![]() |
N. Fujii, T. Nozawa, A. Igawa, B.-i. Kato, N. Igarashi, M. Nonomura, H. Asanoi, S. Tazawa, M. Inoue, and H. Inoue Saturated glucose uptake capacity and impaired fatty acid oxidation in hypertensive hearts before development of heart failure Am J Physiol Heart Circ Physiol, August 1, 2004; 287(2): H760 - H766. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. V. Simoes, S. Egert, S. Ziegler, M. Miyagawa, S. Reder, T. Lehner, N. Nguyen, M. J. Charron, and M. Schwaiger Delayed response of insulin-stimulated fluorine-18 deoxyglucose uptake in glucose transporter-4-null mice hearts J. Am. Coll. Cardiol., May 5, 2004; 43(9): 1690 - 1697. [Abstract] [Full Text] [PDF] |
||||
![]() |
Y. H. Zhang and J. C. Hancox A Novel, Voltage-Dependent Nonselective Cation Current Activated by Insulin in Guinea Pig Isolated Ventricular Myocytes Circ. Res., April 18, 2003; 92(7): 765 - 768. [Abstract] [Full Text] [PDF] |
||||
![]() |
I. Friehs and P. J. del Nido Increased susceptibility of hypertrophied hearts to ischemic injury Ann. Thorac. Surg., February 1, 2003; 75(2): S678 - 684. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. Liao, M. Jain, L. Cui, J. D'Agostino, F. Aiello, I. Luptak, S. Ngoy, R. M. Mortensen, and R. Tian Cardiac-Specific Overexpression of GLUT1 Prevents the Development of Heart Failure Attributable to Pressure Overload in Mice Circulation, October 15, 2002; 106(16): 2125 - 2131. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. Iozzo, P. Chareonthaitawee, D. Dutka, D. J. Betteridge, E. Ferrannini, and P. G. Camici Independent Association of Type 2 Diabetes and Coronary Artery Disease With Myocardial Insulin Resistance Diabetes, October 1, 2002; 51(10): 3020 - 3024. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. Tian and E. D. Abel Responses of GLUT4-Deficient Hearts to Ischemia Underscore the Importance of Glycolysis Circulation, June 19, 2001; 103(24): 2961 - 2966. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. F. Allard, R. B. Wambolt, S. L. Longnus, M. Grist, C. P. Lydell, H. L. Parsons, B. Rodrigues, J. L. Hall, W. C. Stanley, and G. P. Bondy Hypertrophied rat hearts are less responsive to the metabolic and functional effects of insulin Am J Physiol Endocrinol Metab, September 1, 2000; 279(3): E487 - E493. [Abstract] [Full Text] [PDF] |
||||
![]() |
Y. Shimoni, D. Severson, and H. S. Ewart Insulin resistance and the modulation of rat cardiac K+ currents Am J Physiol Heart Circ Physiol, August 1, 2000; 279(2): H639 - H649. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. Iozzo, P. Chareonthaitawee, M. Di Terlizzi, D. J. Betteridge, E. Ferrannini, and P. G. Camici Regional myocardial blood flow and glucose utilization during fasting and physiological hyperinsulinemia in humans Am J Physiol Endocrinol Metab, May 1, 2002; 282(5): E1163 - E1171. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Asakawa, H. Takano, T. Nagai, H. Uozumi, H. Hasegawa, N. Kubota, T. Saito, Y. Masuda, T. Kadowaki, and I. Komuro Peroxisome Proliferator-Activated Receptor {gamma} Plays a Critical Role in Inhibition of Cardiac Hypertrophy In Vitro and In Vivo Circulation, March 12, 2002; 105(10): 1240 - 1246. [Abstract] [Full Text] [PDF] |
||||












