The DOI matches its Crossref record; 39 of the 39 references it cites were found in a registry or an index.
Thiazolidinediones, Like Metformin, Inhibit Respiratory Complex I
Open accessAbstract
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.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“The clinically used drugs with known PGC-1α-modulating activity, such as fibrates, thiazolidinediones, metformin, and statins, display neurotoxicity and a limited ability to cross the blood–brain barrier (BBB) [35,36,37,38].”
From Protective Effects of PGC-1α Activators on Ischemic Stroke in a Rat Model of Photochemically Induced Thrombosis (2021) · cites this paper as [36]
Citations
Cites
Role of AMP-Activated Protein Kinase in Mechanism of Metformin Action
Zhou, G., Myers, R., Li, Y., Chen, Y., Shen, X., Fenyk-Melody, J., Wu, M., Ventre, J., Doebber, T., Fujii, N., et al. (2001) · Journal of Clinical Investigation · doi:10.1172/jci13505 · Cited by 5,652
Yamauchi, T., Kamon, J., Waki, H., Terauchi, Y., Kubota, N., Hara, K., Mori, Y., Ide, T., Murakami, K., Tsuboyama-Kasaoka, N., et al. (2001) · Nature Medicine · doi:10.1038/90984 · Cited by 4,915
Yamauchi, T., Kamon, J., Minokoshi, Y., Ito, Y., Waki, H., Uchida, S., Yamashita, S., Noda, M., Kita, S., Ueki, K., et al. (2002) · Nature Medicine · doi:10.1038/nm788 · Cited by 4,238
OWEN, M. R., DORAN, E., & HALESTRAP, A. P. (2000) · Biochemical Journal · doi:10.1042/bj3480607 · Cited by 2,157
El-Mir, M.-Y., Nogueira, V., Fontaine, E., Avéret, N., Rigoulet, M., & Leverve, X. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.1.223 · Cited by 1,399
PPARγ: a Nuclear Regulator of Metabolism, Differentiation, and Cell Growth
Rosen, E. D., & Spiegelman, B. M. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.r100034200 · Cited by 1,178
Fryer, L. G. D., Patel, A. P., & Carling, D. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m202489200 · Cited by 1,035
Tomas, E., Tsao, T.-S., Saha, A. K., Murrey, H. E., Zhang, C. C., Itani, S. I., Lodish, H. F., & Ruderman, N. B. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.222657499 · Cited by 973
Mu, J., Brozinick, J. T., Valladares, O., Bucan, M., & Birnbaum, M. J. (2001) · Molecular Cell · doi:10.1016/s1097-2765(01)00251-9 · Cited by 924
Musi, N., Hirshman, M. F., Nygren, J., Svanfeldt, M., Bavenholm, P., Rooyackers, O., Zhou, G., Williamson, J. M., Ljunqvist, O., Efendic, S., et al. (2002) · Diabetes · doi:10.2337/diabetes.51.7.2074 · Cited by 806
Cited by
Sorted by citations
Kahn, B. B., Alquier, T., Carling, D., & Hardie, D. G. (2005) · Cell Metabolism · doi:10.1016/j.cmet.2004.12.003 · Cited by 2,799
Cellular and molecular mechanisms of metformin: an overview
Viollet, B., Guigas, B., Garcia, N. S., Leclerc, J., Foretz, M., & Andreelli, F. (2012) · Clinical Science · doi:10.1042/cs20110386 · Cited by 1,720
Metformin: from mechanisms of action to therapies
Foretz, M., Guigas, B., Bertrand, L., Pollak, M., & Viollet, B. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.09.018 · Cited by 1,501
Metformin improves healthspan and lifespan in mice
Martin-Montalvo, A., Mercken, E. M., Mitchell, S. J., Palacios, H. H., Mote, P. L., Scheibye-Knudsen, M., Gomes, A. P., Ward, T. M., Minor, R. K., Blouin, M.-J., et al. (2013) · Nature Communications · doi:10.1038/ncomms3192 · Cited by 1,445
The AMP-activated protein kinase pathway – new players upstream and downstream
Hardie, D. G. (2004) · Journal of Cell Science · doi:10.1242/jcs.01540 · Cited by 1,163
Metadata
- 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
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2004-04-01
- Volume
- 53
- Issue
- 4
- Pages
- 1052-1059
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
