Mitochondrial Respiration Is Decreased in Skeletal Muscle of Patients With Type 2 Diabetes
Mitochondrial Respiration Is Decreased in Skeletal Muscle of Patients With Type 2 Diabetes Martin Mogensen 1 , Kent Sahlin 1 2 3 , Maria Fernström 2 3 , Dorte Glintborg 4 , Birgitte F. Vind 4 , Henning Beck-Nielsen 4 and Kurt Højlund 4 1 Institute of Sports Science and Clinical Biomechanics, Univers...
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Published in | Diabetes (New York, N.Y.) Vol. 56; no. 6; pp. 1592 - 1599 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
Alexandria, VA
American Diabetes Association
01.06.2007
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Subjects | |
Online Access | Get full text |
ISSN | 0012-1797 1939-327X 1939-327X |
DOI | 10.2337/db06-0981 |
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Summary: | Mitochondrial Respiration Is Decreased in Skeletal Muscle of Patients With Type 2 Diabetes
Martin Mogensen 1 ,
Kent Sahlin 1 2 3 ,
Maria Fernström 2 3 ,
Dorte Glintborg 4 ,
Birgitte F. Vind 4 ,
Henning Beck-Nielsen 4 and
Kurt Højlund 4
1 Institute of Sports Science and Clinical Biomechanics, University of Southern Denmark, Odense, Denmark
2 Stockholm University College of Physical Education and Sports, GIH, Stockholm, Sweden
3 Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden
4 Department of Endocrinology, Diabetes Research Centre, Odense University Hospital, Odense, Denmark
Address correspondence and reprint requests to Kurt Højlund, MD, PhD, Diabetes Research Centre, Department of Endocrinology,
Odense University Hospital, Kloevervaenget 6, 3, DK-5000 Odense C, Denmark. E-mail: k.hojlund{at}dadlnet.dk
Abstract
We tested the hypothesis of a lower respiratory capacity per mitochondrion in skeletal muscle of type 2 diabetic patients
compared with obese subjects. Muscle biopsies obtained from 10 obese type 2 diabetic and 8 obese nondiabetic male subjects
were used for assessment of 3-hydroxy-Acyl-CoA-dehydrogenase (HAD) and citrate synthase activity, uncoupling protein (UCP)3
content, oxidative stress measured as 4-hydroxy-2-nonenal (HNE), fiber type distribution, and respiration in isolated mitochondria.
Respiration was normalized to citrate synthase activity (mitochondrial content) in isolated mitochondria. Maximal ADP-stimulated
respiration (state 3) with pyruvate plus malate and respiration through the electron transport chain (ETC) were reduced in
type 2 diabetic patients, and the proportion of type 2X fibers were higher in type 2 diabetic patients compared with obese
subjects (all P < 0.05). There were no differences in respiration with palmitoyl- l -carnitine plus malate, citrate synthase activity, HAD activity, UCP3 content, or oxidative stress measured as HNE between
the groups. In the whole group, state 3 respiration with pyruvate plus malate and respiration through ETC were negatively
associated with A1C, and the proportion of type 2X fibers correlated with markers of insulin resistance ( P < 0.05). In conclusion, we provide evidence for a functional impairment in mitochondrial respiration and increased amount
of type 2X fibers in muscle of type 2 diabetic patients. These alterations may contribute to the development of type 2 diabetes
in humans with obesity.
ETC, electron transport chain
FFA, free fatty acid
HAD, 3-hydroxy-Acyl-CoA-dehydrogenase
HNE, 4-hydroxy-2-nonenal
HOMA-IR, homeostasis model assessment of insulin resistance
RCI, respiratory control index
ROS, reactive oxygen species
UCP, uncoupling protein
Footnotes
Published ahead of print at http://diabetes.diabetesjournals.org on 9 March 2007. DOI: 10.2337/db06-0981.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore
be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Accepted February 26, 2007.
Received July 17, 2006.
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 |
ISSN: | 0012-1797 1939-327X 1939-327X |
DOI: | 10.2337/db06-0981 |