Altered Fiber Distribution and Fiber-Specific Glycolytic and Oxidative Enzyme Activity in Skeletal Muscle of Patients With Type 2 Diabetes
- Andreas Oberbach12,
- Yvonne Bossenz2,
- Stefanie Lehmann2,
- Josef Niebauer, MD, PHD3,
- Volker Adams, PHD4,
- Ralf Paschke, MD5,
- Michael R. Schön, MD6,
- Matthias Blüher, MD25 and
- Karla Punkt, PHD1
- 1Institute of Anatomy, University of Leipzig, Germany
- 2Junior Research Group N03, Interdisciplinary Centre for Clinical Research (IZKF) Leipzig, University of Leipzig, Leipzig, Germany
- 3Institute of Sports Medicine, Paracelsus Private Medical University, Salzburg, Austria
- 4Heart Center, Department of Cardiology, University of Leipzig, Leipzig, Germany
- 5Department of Medicine III, University of Leipzig, Germany
- 6Department of Surgery, University of Leipzig, Germany
- Address correspondence and reprint requests to Prof. Dr. med. M. Blüher, University of Leipzig, IZKF Leipzig, Junior Research Group N03, Inselstr. 22, D-04103 Leipzig, Germany. E-mail: bluma{at}medizin.uni-leipzig.de
Abstract
OBJECTIVE—We investigated whether alterations of glycolytic and oxidative enzyme capacity in skeletal muscle of patients with type 2 diabetes pertain to specific muscle fibers and are associated with changes in muscle fiber composition.
RESEARCH DESIGN AND METHODS—Vastus lateralis muscle was obtained by percutaneous biopsy from 10 patients with type 2 diabetes and 15 age- and BMI-matched healthy volunteers. Using cytophotometry, muscle fiber composition and fiber type–specific glycolytic and oxidative enzyme activities were measured in slow oxidative, fast oxidative glycolytic, and fast glycolytic fibers.
RESULTS—In the whole muscle, oxidative activity was decreased in patients with type 2 diabetes. The slow oxidative fiber fraction was reduced by 16%, whereas the fast glycolytic fiber fraction was increased by 49% in skeletal muscle from the diabetic patients. Both oxidative and glycolytic enzyme activities were significantly increased in fast glycolytic and fast oxidative glycolytic fibers of type 2 diabetic patients. However, the fiber-specific ratio of glycolytic enzyme activity relative to oxidative activity was not different between type 2 diabetic patients and the control subjects. The myofibrillic ATP activity was significantly lower in all fiber types of patients with type 2 diabetes and correlates with glucose infusion rate during the steady state of a euglycemic-hyperinsulinemic clamp and maximal aerobic capacity and negatively with HbA1c values.
CONCLUSIONS—Reduced oxidative enzyme activity in muscle of type 2 diabetic patients is most likely due to a reduction in slow oxidative fibers. Increased glycolytic and oxidative enzyme activities in individual muscle fibers are closely related to measures of long-term glycemic control and whole-body insulin sensitivity and could therefore represent a compensatory mechanism of the muscle in function of the altered glucose metabolism.
- GPDH, glycerol-3-phosphate dehydrogenase
- LDH, lactate dehydrogenase
- NGT, normal glucose tolerant
- SDH, succinate dehydrogenase
Footnotes
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A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.
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.
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- Accepted December 25, 2006.
- Received October 1, 2005.
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