Metallothionein-mediated antioxidant defense system and its response to exercise training are impaired in human type 2 diabetes

Celena Scheede-Bergdahl, Milena Penkowa, Juan Hidalgo, David B. Olsen, Peter Schjerling, Clara Prats, Robert Boushel, Flemming Dela

Research output: Contribution to journalArticleResearchpeer-review

37 Citations (Scopus)

Abstract

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. © 2005 by the American Diabetes Association.
Original languageEnglish
Pages (from-to)3089-3094
JournalDiabetes
Volume54
Issue number11
DOIs
Publication statusPublished - 1 Nov 2005

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