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Diabetes 54:3089-3094, 2005
© 2005 by the American Diabetes Association, Inc.

Metallothionein-Mediated Antioxidant Defense System and Its Response to Exercise Training Are Impaired in Human Type 2 Diabetes

Celena Scheede-Bergdahl1, Milena Penkowa2, Juan Hidalgo3, David B. Olsen1, Peter Schjerling4, Clara Prats1, Robert Boushel5, and Flemming Dela1

1 Copenhagen Muscle Research Center, The Panum Institute, Department of Medical Physiology, University of Copenhagen, Copenhagen, Denmark
2 Centre of Inflammation and Metabolism, Department of Medical Anatomy at the Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
3 Institute of Neurosciences and Department of Cellular Biology, Physiology and Immunology, Animal Physiology Unit, Faculty of Sciences, Autonomous University of Barcelona, Barcelona, Spain
4 Copenhagen Muscle Research Centre, Department of Molecular Muscle Biology, Rigshospitalet, Copenhagen, Denmark
5 Department of Exercise Science, Concordia University, Montréal, Canada

Oxidative stress is implicated in diabetes complications, during which endogenous antioxidant defenses have important pathophysiological consequences. To date, the significance of endogenous antioxidants such as metallothioneins I and II (MT-I+II) in type 2 diabetes remains unclear. To examine the MT-I+II–mediated antioxidant capacity and its response to exercise training in the skeletal muscle of patients with type 2 diabetes, biopsies and blood samples were taken from 13 matched subjects (type 2 diabetes n = 8, control subjects n = 5) both before and after 8 weeks of exercise training. Immunohistochemical analysis revealed reduced MT-I+II levels in the skeletal muscle of type 2 diabetic subjects compared with control subjects. Control subjects produced a robust increase of MT-I+II in response to training; however, in type 2 diabetes, MT-I+II levels remained essentially unchanged. Significantly lower levels of MT-I+II were also detected in the plasma of type 2 diabetic subjects compared with control subjects. These results suggest that, in control subjects, the MT-I+II defense system is active and inducible within skeletal muscle tissue and plasma. In type 2 diabetes, reduced levels of MT-I+II in muscle and plasma, as well as the deficient MT-I+II response to exercise, indicate that this antioxidant defense is impaired. This study presents a novel candidate in the pathogenesis of complications related to oxidative stress in type 2 diabetes.

Address correspondence and reprint requests to Celena Scheede-Bergdahl, The Copenhagen Muscle Research Centre, The Panum Institute, Department of Medical Physiology, University of Copenhagen, Blegdamsvej 3, DK 2200 Copenhagen N, Denmark. E-mail: celena{at}mfi.ku.dk

Abbreviations: GSH, glutathione; MDA, malondialdehyde; MT-I+II, metallothioneins I and II; NITT, nitrotyrosine; ROS, reactive oxygen species; SOD, superoxide dismutase


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Diabetes Diabetes Care Clinical Diabetes Diabetes Spectrum
Copyright © 2005 by the American Diabetes Association.