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Submitted on July 14, 2005
Accepted on December 19, 2005
Departments of Human Biology and Movement Sciences, Maastricht University; Department of Endocrinology, Academic Hospital Maastricht; Clinique Romande de Readaptation SUVA Care, Sion, Switzerland
* To whom correspondence should be addressed. E-mail: p.schrauwen{at}hb.unimaas.nl.
Context: The mitochondrial uncoupling protein-3 has been implicated in the protection of the mitochondrial matrix against lipid-induced mitochondrial damage. Recent evidence points toward mitochondrial aberrations as a major contributor to the development of insulin resistance and diabetes, and UCP3 is reduced in diabetes.
Objective: We compared skeletal muscle UCP3 protein levels in pre-diabetic subjects (i.e. impaired glucose tolerance, IGT), diabetic patients and healthy controls and examined whether rosiglitazone treatment was able to restore UCP3.
Patients, design, intervention: Ten middle-aged obese men with type 2 diabetes mellitus (age 61.4 ± 3.1 yr.; BMI 29.8 ± 2.9 kg/m2), nine IGT subjects (age 59.0 ± 6.6 yr.; BMI 29.7 ± 3.0) and ten, age- and BMI-matched, healthy controls (57.3 ± 7.4 yr.; BMI 30.1 ± 3.9 kg/m2) participated in this study. After baseline comparisons, diabetic patients received rosiglitazone (2*4 mg/day) for 8 weeks.
Main Outcome Measures: Muscle biopsies were sampled to determine UCP3 and mitochondrial protein (complex I to V) content.
Results: UCP3 protein content was significantly lower in pre-diabetic IGT subjects and in diabetic patients compared with healthy controls (39.0 ± 28.5, 47.2 ± 24.7 and 72.0 ± 23.7 AU resp., P < 0.05) whereas the levels of the mitochondrial protein complex I to V were similar between groups. Rosiglitazone treatment for 8 weeks significantly increased insulin sensitivity and muscle UCP3 content (from 53.2 ± 29.9 to 66.3 ± 30.9 AU, P < 0.05).
Conclusion: We show that UCP3 protein content is reduced in pre-diabetic subjects and type 2 diabetic patients. Eight weeks of rosiglitazone treatment restores skeletal muscle UCP3 protein in diabetic patients.
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