Based on available evidence, we would propose the following. (i) Excesses of glucose and free fatty acids cause insulin resistance in skeletal muscle and damage to the endothelial cell by a similar mechanism. (ii) Key pathogenetic events in this mechanism very likely include increased fatty acid esterification, protein kinase C activation, an increase in oxidative stress (demonstrated to date in endothelium) and alterations in the inhibitor κB kinase/nuclear factor κB system. (iii) Activation of AMP-activated protein kinase (AMPK) inhibits all of these events and enhances insulin signalling in the endothelial cell. It also enhances insulin action in muscle; however, the mechanism by which it does so has not been well studied. (iv) The reported beneficial effects of exercise and metformin on cardiovascular disease and insulin resistance in humans could be related to the fact that they activate AMPK. (v) The comparative roles of AMPK in regulating metabolism, signalling and gene expression in muscle and endothelial cells warrant further study.
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February 2003
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Conference Article|
February 01 2003
Malonyl-CoA and AMP-activated protein kinase (AMPK): possible links between insulin resistance in muscle and early endothelial cell damage in diabetes
N.B. Ruderman;
N.B. Ruderman
1
*Diabetes Unit, Section of Endocrinology and Departments of Medicine and Physiology, Boston University Medical Center, Boston, MA 02118, U.S.A.
1To whom correspondence should be addressed (e-mail nruderman@medicine.bu.edu).
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J.M. Cacicedo;
J.M. Cacicedo
*Diabetes Unit, Section of Endocrinology and Departments of Medicine and Physiology, Boston University Medical Center, Boston, MA 02118, U.S.A.
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S. Itani;
S. Itani
*Diabetes Unit, Section of Endocrinology and Departments of Medicine and Physiology, Boston University Medical Center, Boston, MA 02118, U.S.A.
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N. Yagihashi;
N. Yagihashi
*Diabetes Unit, Section of Endocrinology and Departments of Medicine and Physiology, Boston University Medical Center, Boston, MA 02118, U.S.A.
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A.K. Saha;
A.K. Saha
*Diabetes Unit, Section of Endocrinology and Departments of Medicine and Physiology, Boston University Medical Center, Boston, MA 02118, U.S.A.
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K. Chen;
K. Chen
‡Division of Cardiology, Boston University Medical Center, Boston MA 02118, U.S.A.
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M. Zou;
M. Zou
§Vascular Biology Unit, Boston University Medical Center, Boston MA 02118, U.S.A.
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D. Carling;
D. Carling
¶Cellular Stress Unit, MRC Clinical Sciences Center, Hammersmith Hospital, London W12 ONN, U.K.
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G. Boden;
G. Boden
∥Clinical Research Center, Temple University, School of Medicine, Philadelphia, PA, U.S.A.
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R.A. Cohen;
R.A. Cohen
¶Cellular Stress Unit, MRC Clinical Sciences Center, Hammersmith Hospital, London W12 ONN, U.K.
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J. Keaney;
J. Keaney
‡Division of Cardiology, Boston University Medical Center, Boston MA 02118, U.S.A.
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E.W. Kraegen;
E.W. Kraegen
†Garvan Institute, Sydney, Australia
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Y. Ido
Y. Ido
*Diabetes Unit, Section of Endocrinology and Departments of Medicine and Physiology, Boston University Medical Center, Boston, MA 02118, U.S.A.
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Publisher: Portland Press Ltd
Online ISSN: 1470-8752
Print ISSN: 0300-5127
Copyright 2003 Biochemical Society
2003
Biochem Soc Trans (2003) 31 (1): 202–206.
Citation
N.B. Ruderman, J.M. Cacicedo, S. Itani, N. Yagihashi, A.K. Saha, J.M. Ye, K. Chen, M. Zou, D. Carling, G. Boden, R.A. Cohen, J. Keaney, E.W. Kraegen, Y. Ido; Malonyl-CoA and AMP-activated protein kinase (AMPK): possible links between insulin resistance in muscle and early endothelial cell damage in diabetes. Biochem Soc Trans 1 February 2003; 31 (1): 202–206. doi: https://doi.org/10.1042/bst0310202
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