title: Metallothionein-mediated antioxidant defense system and its response to exercise training are impaired in human type 2 diabetes.
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.
authors.affiliation: The Copenhagen Muscle Research Centre, The Panum Institute, Department of Medical Physiology, University of Copenhagen, Blegdamsvej 3, DK 2200 Copenhagen N, Denmark. celena@mfi.ku.dk
authors.forename: Celena
authors.initials: C
authors.lastname: Scheede-Bergdahl
authors.forename: Milena
authors.initials: M
authors.lastname: Penkowa
authors.forename: Juan
authors.initials: J
authors.lastname: Hidalgo
authors.forename: David B
authors.initials: DB
authors.lastname: Olsen
authors.forename: Peter
authors.initials: P
authors.lastname: Schjerling
authors.forename: Clara
authors.initials: C
authors.lastname: Prats
authors.forename: Robert
authors.initials: R
authors.lastname: Boushel
authors.forename: Flemming
authors.initials: F
authors.lastname: Dela
mesh_terms: D000975:Antioxidants / Q000378:metabolism*; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D015444:Exercise / Q000502:physiology*; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D008668:Metallothionein / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism; D018384:Oxidative Stress; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D000975:Antioxidants; D012333:RNA, Messenger; D008668:Metallothionein