Cited by 524Metabolism, Diabetes, and CancerMitochondrial Function and PathologyDiabetes Treatment and Management

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Thiazolidinediones, Like Metformin, Inhibit Respiratory Complex I

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Brunmair, Barbara, Staniek, Katrin, Gras, Florian, Scharf, Nicole, Althaym, Aleksandra, Clara, Renate, Roden, Michael, Gnaiger, Erich, Nohl, Hans, Waldhäusl, Werner, Fürnsinn, Clemens·2004·Diabetes

DOI 10.2337/diabetes.53.4.1052

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Abstract

Metformin and thiazolidinediones (TZDs) are believed to exert their antidiabetic effects via different mechanisms. As evidence suggests that both impair cell respiration in vitro, this study compared their effects on mitochondrial functions. The activity of complex I of the respiratory chain, which is known to be affected by metformin, was measured in tissue homogenates that contained disrupted mitochondria. In homogenates of skeletal muscle, metformin and TZDs reduced the activity of complex I (30 mmol/l metformin, −15 ± 2%; 100 μmol/l rosiglitazone, −54 ± 7; and 100 μmol/l pioglitazone, −12 ± 4; P < 0.05 each). Inhibition of complex I was confirmed by reduced state 3 respiration of isolated mitochondria consuming glutamate + malate as substrates for complex I (30 mmol/l metformin, −77 ± 1%; 100 μmol/l rosiglitazone, −24 ± 4; and 100 μmol/l pioglitazone, −18 ± 5; P < 0.05 each), whereas respiration with succinate feeding into complex II was unaffected. In line with inhibition of complex I, 24-h exposure of isolated rat soleus muscle to metformin or TZDs reduced cell respiration and increased anaerobic glycolysis (glucose oxidation: 270 μmol/l metformin, −30 ± 9%; 9 μmol/l rosiglitazone, −25 ± 8; and 9 μmol/l pioglitazone, −45 ± 3; lactate release: 270 μmol/l metformin, +84 ± 12; 9 μmol/l rosiglitazone, +38 ± 6; and 9 μmol/l pioglitazone, +64 ± 11; P < 0.05 each). As both metformin and TZDs inhibit complex I activity and cell respiration in vitro, similar mitochondrial actions could contribute to their antidiabetic effects.

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Authors: Brunmair, B., Staniek, K., Gras, F., Scharf, N., Althaym, A., Clara, R., Roden, M., Gnaiger, E., Nohl, H., Waldhäusl, W., & Fürnsinn, C.
Affiliations: University of Vienna (AT)
University of Veterinary Medicine Vienna (AT)
Universität Innsbruck (AT)
Department of Medicine III, Division of Endocrinology & Metabolism, University of Vienna, Vienna, Austria
ORCID: Brunmair, Barbara
Roden, Michael
Gnaiger, Erich
Venue: Diabetes
Publisher: American Diabetes Association
Published: 2004-04-01
Volume: 53
Issue: 4
Pages: 1052-1059
ISSN: 0012-1797 (ISSN-L)
1939-327X
DOI: 10.2337/diabetes.53.4.1052
OpenAlex: W2403578638
Cited by: 521
References: 39
Citations by year: 2026: 6 · 2025: 9 · 2024: 15 · 2023: 10 · 2022: 14 · 2021: 15 · 2020: 33 · 2019: 25 · 2018: 16 · 2017: 27 · 2016: 37 · 2015: 30 · 2014: 40 · 2013: 33 · 2012: 29
FWCI: 7.64
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Diabetes (publishedVersion)
PubMed (publishedVersion)
Funders: Pfizer
Austrian Science Fund
Universität Wien
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
Keywords: thiazolidinediones, metformin, mitochondrial complex I, mitochondrial respiration, rosiglitazone, pioglitazone, skeletal muscle, anaerobic glycolysis, glucose oxidation, lactate release, antidiabetic mechanism, type 2 diabetes
MeSH terms: Rosiglitazone, Pioglitazone, Animals, Energy Metabolism, Hypoglycemic Agents, Male, Metformin, Mitochondria, Oxygen Consumption, Potassium Chloride, Rotenone, Rats, Sprague-Dawley, Muscle, Skeletal, Electron Transport Complex I, Thiazolidinediones, Rats

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Thiazolidinediones, Like Metformin, Inhibit Respiratory Complex I

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