Improvement of Cardiac Functions by Chronic Metformin Treatment Is Associated With Enhanced Cardiac Autophagy in Diabetic OVE26 Mice
Open accessAbstract
OBJECTIVE: Autophagy is a critical cellular system for removal of aggregated proteins and damaged organelles. Although dysregulated autophagy is implicated in the development of heart failure, the role of autophagy in the development of diabetic cardiomyopathy has not been studied. We investigated whether chronic activation of the AMP-activated protein kinase (AMPK) by metformin restores cardiac function and cardiomyocyte autophagy in OVE26 diabetic mice. RESEARCH DESIGN AND METHODS: OVE26 mice and cardiac-specific AMPK dominant negative transgenic (DN)-AMPK diabetic mice were treated with metformin or vehicle for 4 months, and cardiac autophagy, cardiac functions, and cardiomyocyte apoptosis were monitored. RESULTS: Compared with control mice, diabetic OVE26 mice exhibited a significant reduction of AMPK activity in parallel with reduced cardiomyocyte autophagy and cardiac dysfunction in vivo and in isolated hearts. Furthermore, diabetic OVE26 mouse hearts exhibited aggregation of chaotically distributed mitochondria between poorly organized myofibrils and increased polyubiquitinated protein and apoptosis. Inhibition of AMPK by overexpression of a cardiac-specific DN-AMPK gene reduced cardiomyocyte autophagy, exacerbated cardiac dysfunctions, and increased mortality in diabetic mice. Finally, chronic metformin therapy significantly enhanced autophagic activity and preserved cardiac functions in diabetic OVE26 mice but not in DN-AMPK diabetic mice. CONCLUSIONS: Decreased AMPK activity and subsequent reduction in cardiac autophagy are important events in the development of diabetic cardiomyopathy. Chronic AMPK activation by metformin prevents cardiomyopathy by upregulating autophagy activity in diabetic OVE26 mice. Thus, stimulation of AMPK may represent a novel approach to treat diabetic cardiomyopathy.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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 OVE26 diabetic mice, isolated hearts showed a substantial reduction in AMPK function and cardiomyocyte autophagy as well as mitochondria aggregations and increased apoptosis that was reversed following chronic treatment with metformin.
“Isolated hearts, from the diabetic mice showed a substantial reduction in AMPK function and cardiomyocyte autophagy as well as mitochondria aggregations dispersed between poorly organized myofibrils and increased apoptosis that was reversed following chronic treatment with metformin (231).”
From A Critical Review of the Evidence That Metformin Is a Putative Anti-Aging Drug That Enhances Healthspan and Extends Lifespan (2021) · cites this paper as [231]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
1 retracted
Xie, Z., Zhang, J., Wu, J., Viollet, B., & Zou, M. (2008) · Diabetes · doi:10.2337/db08-0610 · Cited by 163 · see citing works
Self-citationRetractedStratton, I. M. (2000) · BMJ · doi:10.1136/bmj.321.7258.405 · Cited by 9,059 · see citing works
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 · see citing works
TSC2 Mediates Cellular Energy Response to Control Cell Growth and Survival
Inoki, K., Zhu, T., & Guan, K.-L. (2003) · Cell · doi:10.1016/s0092-8674(03)00929-2 · Cited by 3,914 · see citing works
Autophagy as a regulated pathway of cellular degradation.
Klionsky, D., & Emr, S. (2000) · Science · doi:10.1126/science.290.5497.1717 · Cited by 3,794 · see citing works
Levine, B., & Klionsky, D. J. (2004) · Developmental Cell · doi:10.1016/s1534-5807(04)00099-1 · Cited by 3,671 · see citing works
Induction of autophagy and inhibition of tumorigenesis by beclin 1
Liang, X. H., Jackson, S., Seaman, M., Brown, K., Kempkes, B., Hibshoosh, H., & Levine, B. (1999) · Nature · doi:10.1038/45257 · Cited by 3,347 · see citing works
Selective degradation of mitochondria by mitophagy
Kim, I., Rodriguez-Enriquez, S., & Lemasters, J. J. (2007) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2007.03.034 · Cited by 1,558 · see citing works
Claycomb, W. C., Lanson, N. A., Stallworth, B. S., Egeland, D. B., Delcarpio, J. B., Bahinski, A., & Izzo, N. J. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.6.2979 · Cited by 1,546 · see citing works
Diabetic Cardiomyopathy Revisited
Boudina, S., & Abel, E. D. (2007) · Circulation · doi:10.1161/circulationaha.106.679597 · Cited by 1,543 · see citing works
The role of autophagy in cardiomyocytes in the basal state and in response to hemodynamic stress
Nakai, A., Yamaguchi, O., Takeda, T., Higuchi, Y., Hikoso, S., Taniike, M., Omiya, S., Mizote, I., Matsumura, Y., Asahi, M., et al. (2007) · Nature Medicine · doi:10.1038/nm1574 · Cited by 1,520 · see citing works
Matsui, Y., Takagi, H., Qu, X., Abdellatif, M., Sakoda, H., Asano, T., Levine, B., & Sadoshima, J. (2007) · Circulation Research · doi:10.1161/01.res.0000261924.76669.36 · Cited by 1,505 · see citing works
Autophagy inhibition enhances therapy-induced apoptosis in a Myc-induced model of lymphoma
Amaravadi, R. K., Yu, D., Lum, J. J., Bui, T., Christophorou, M. A., Evan, G. I., Thomas‐Tikhonenko, A., & Thompson, C. B. (2007) · Journal of Clinical Investigation · doi:10.1172/jci28833 · Cited by 1,136 · see citing works
Kirpichnikov, D., McFarlane, S. I., & Sowers, J. R. (2002) · Annals of Internal Medicine · doi:10.7326/0003-4819-137-1-200207020-00009 · Cited by 1,084 · see citing works
Shibata, R., Sato, K., Pimentel, D. R., Takemura, Y., Kihara, S., Ohashi, K., Funahashi, T., Ouchi, N., & Walsh, K. (2005) · Nature Medicine · doi:10.1038/nm1295 · Cited by 982 · see citing works
Autophagy in metazoans: cell survival in the land of plenty
Lum, J., DeBerardinis, R., & Thompson, C. (2005) · Nature reviews. Molecular cell biology · doi:10.1038/nrm1660 · Cited by 842 · see citing works
Russell, R. R., Li, J., Coven, D. L., Pypaert, M., Zechner, C., Palmeri, M., Giordano, F. J., Mu, J., Birnbaum, M. J., & Young, L. H. (2004) · Journal of Clinical Investigation · doi:10.1172/jci19297 · Cited by 738 · see citing works
Adiponectin-mediated modulation of hypertrophic signals in the heart
Shibata, R., Ouchi, N., Ito, M., Kihara, S., Shiojima, I., Pimentel, D. R., Kumada, M., Sato, K., Schiekofer, S., Ohashi, K., et al. (2004) · Nature Medicine · doi:10.1038/nm1137 · Cited by 671 · see citing works
Autophagy in chronically ischemic myocardium
Yan, L., Vatner, D. E., Kim, S., Ge, H., Masurekar, M. R., Massover, W. H., Yang, G., Matsui, Y., Sadoshima, J., & Vatner, S. F. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0506843102 · Cited by 497 · see citing works
AMP-activated Protein Kinase and the Regulation of Autophagic Proteolysis
Meley, D., Bauvy, C., Houben-Weerts, J. H. P. M., Dubbelhuis, P. F., Helmond, M. T. J., Codogno, P., & Meijer, A. J. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m605488200 · Cited by 461 · see citing works
Calvert, J. W., Gundewar, S., Jha, S., Greer, J. J. M., Bestermann, W. H., Tian, R., & Lefer, D. J. (2008) · Diabetes · doi:10.2337/db07-1098 · Cited by 422 · see citing works
Self-citationWhite, S. M., Constantin, P. E., & Claycomb, W. C. (2004) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00986.2003 · Cited by 410 · see citing works
Tian, R., Musi, N., D’Agostino, J., Hirshman, M. F., & Goodyear, L. J. (2001) · Circulation · doi:10.1161/hc4001.097183 · Cited by 308 · see citing works
Self-citationXie, Z., Dong, Y., Scholz, R., Neumann, D., & Zou, M.-H. (2008) · Circulation · doi:10.1161/circulationaha.107.744490 · Cited by 273 · see citing works
Self-citationCardiac mitochondrial damage and biogenesis in a chronic model of type 1 diabetes
Shen, X., Zheng, S., Thongboonkerd, V., Xu, M., Pierce, W. M., Klein, J. B., & Epstein, P. N. (2004) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00047.2004 · Cited by 258 · see citing works
Kaniuk, N. A., Kiràly, M. A., Bates, H. E., Vranić, M., Volchuk, A., & Brumell, J. H. (2007) · Diabetes · doi:10.2337/db06-1160 · Cited by 222 · see citing works
Xing, Y., Musi, N., FUJII, N. L., Zou, L., Luptak, I., Hirshman, M. F., Goodyear, L. J., & Tian, R. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m303521200 · Cited by 213 · see citing works
Self-citationOverexpression of Metallothionein Reduces Diabetic Cardiomyopathy
Liang, Q., Carlson, E. C., Donthi, R. V., Kralik, P. M., Shen, X., & Epstein, P. N. (2002) · Diabetes · doi:10.2337/diabetes.51.1.174 · Cited by 182 · see citing works
Adeghate, E. A. (2004) · Molecular and Cellular Biochemistry · doi:10.1023/b:mcbi.0000028755.86521.11 · Cited by 172 · see citing works
Palmitate-mediated Alterations in the Fatty Acid Metabolism of Rat Neonatal Cardiac Myocytes
Hickson-Bick, D. L. M., Buja, L. M., & McMillin, J. B. (2000) · Journal of Molecular and Cellular Cardiology · doi:10.1006/jmcc.1999.1098 · Cited by 170 · see citing works
AMP-Activated Protein Kinase and Autophagy
Meijer, A. J., & Codogno, P. (2007) · Autophagy · doi:10.4161/auto.3710 · Cited by 165 · see citing works
Approaching the Molecular Mechanism of Autophagy
STRØMHAUG, P. E., & Klionsky, D. J. (2001) · Traffic · doi:10.1034/j.1600-0854.2001.20802.x · Cited by 155 · see citing works
Mechanisms of Apoptosis in the Heart
Gustafsson, Å. B., & Gottlieb, R. (2003) · Journal of Clinical Immunology · doi:10.1023/b:joci.0000010421.56035.60 · Cited by 154 · see citing works
Brady, N. R., Hamacher‐Brady, A., Yuan, H., & Gottlieb, R. A. (2007) · The FEBS Journal · doi:10.1111/j.1742-4658.2007.05849.x · Cited by 137 · see citing works
Capano, M., & Crompton, M. (2006) · Biochemical Journal · doi:10.1042/bj20051654 · Cited by 128 · see citing works
Diabetic cardiomyopathy: fact or fiction?
Francis, G. S. (2001) · Heart · doi:10.1136/heart.85.3.247 · Cited by 105 · see citing works
Osteopontin Modulates Myocardial Hypertrophy in Response to Chronic Pressure Overload in Mice
Xie, Z., Singh, M., & Singh, K. (2004) · Hypertension · doi:10.1161/01.hyp.0000148458.03202.48 · Cited by 105 · see citing works
Self-citationXie, Z., Dong, Y., Zhang, J., Scholz, R., Neumann, D., & Zou, M. (2009) · Molecular and Cellular Biology · doi:10.1128/mcb.01417-08 · Cited by 98 · see citing works
Self-citationPicano, E. (2003) · Journal of the American College of Cardiology · doi:10.1016/s0735-1097(03)00647-8 · Cited by 94 · see citing works
Diabetic cardiomyopathy: A metabolic perspective
Avogaro, A., de Kreutzenberg, S. V., Negut, C., et al. (2004) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2003.11.003 · Cited by 93 · see citing works
Finsen, A. V., Christensen, G., & Sjaastad, I. (2004) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00924.2004 · Cited by 83 · see citing works
Metformin improves cardiac function in isolated streptozotocin-diabetic rat hearts
Verma, S., & McNeill, J. H. (1994) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.1994.266.2.h714 · Cited by 60 · see citing works
Metformin Improves Cardiac Functional Recovery After Ischemia in Rats
Legtenberg, R. J., Houston, R. J. F., Oeseburg, B., & Smits, P. (2002) · Hormone and Metabolic Research · doi:10.1055/s-2002-26705 · Cited by 51 · see citing works
He, C., Choi, H. C., & Xie, Z. (2010) · American Journal Of Pathology · doi:10.2353/ajpath.2010.090783 · Cited by 36 · see citing works
Self-citationSong, Y., Du, Y., Prabhu, S. D., & Epstein, P. N. (2007) · The Review of Diabetic Studies · doi:10.1900/rds.2007.4.159 · Cited by 35 · see citing works
Eberli, F. R., Sam, F., Ngoy, S., et al. (1998) · Journal of Molecular and Cellular Cardiology · doi:10.1006/jmcc.1998.0702 · Cited by 29 · see citing works
The direct effects of streptozotocin and alloxan on contractile function in rat heart
Salem, K. A., Kosanović, M., Qureshi, A., et al. (2009) · Pharmacological Research · doi:10.1016/j.phrs.2009.01.003 · Cited by 17 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
MTOR: a pharmacologic target for autophagy regulation
Kim, Y. C., & Guan, K.-L. (2015) · Journal of Clinical Investigation · doi:10.1172/jci73939 · Cited by 2,126 · see citing works
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 · see citing works
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 · see citing works
Metformin as a tool to target aging
Barzilai, N., Crandall, J. P., Kritchevsky, S. B., & Espeland, M. A. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.05.011 · Cited by 1,096 · see citing works
Molecular mechanisms of diabetic cardiomyopathy
Bugger, H., & Abel, E. D. (2014) · Diabetologia · doi:10.1007/s00125-014-3171-6 · Cited by 903 · see citing works
Madeo, F., Carmona-Gutierrez, D., Hofer, S. J., & Kroemer, G. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2019.01.018 · Cited by 630 · see citing works
Tong, M., Saito, T., Zhai, P., Oka, S.-I., Mizushima, W., Nakamura, M., Ikeda, S., Shirakabe, A., & Sadoshima, J. (2019) · Circulation Research · doi:10.1161/circresaha.118.314607 · Cited by 498 · see citing works
Wang, Q., Zhang, M., Torres, G., Wu, S., Ouyang, C., Xie, Z., & Zou, M.-H. (2017) · Diabetes · doi:10.2337/db16-0915 · Cited by 370 · see citing works
Inflammation and metabolic cardiomyopathy
Nishida, K., & Otsu, K. (2017) · Cardiovascular Research · doi:10.1093/cvr/cvx012 · Cited by 329 · see citing works
Autophagy in cardiovascular biology
Lavandero, S., Chiong, M., Rothermel, B. A., & Hill, J. A. (2015) · Journal of Clinical Investigation · doi:10.1172/jci73943 · Cited by 331 · see citing works
Chen, D., Xia, D., Pan, Z., Xu, D., Zhou, Y., Wu, Y., Cai, N., Tang, Q., Wang, C., Yan, M., et al. (2016) · Cell Death & Disease · doi:10.1038/cddis.2016.334 · Cited by 314 · see citing works
Wu, S., Lu, Q., Ding, Y., Wu, Y., Qiu, Y., Wang, P., Mao, X., Huang, K., Xie, Z., & Zou, M.-H. (2019) · Circulation · doi:10.1161/circulationaha.118.033552 · Cited by 298 · see citing works
AMPK, Mitochondrial Function, and Cardiovascular Disease
Wu, S., & Zou, M.-H. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21144987 · Cited by 286 · see citing works
Self-citationMohammed, I., Hollenberg, M. D., Ding, H., & Triggle, C. R. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.718942 · Cited by 278 · see citing works
Nesti, L., & Natali, A. (2017) · Nutrition Metabolism and Cardiovascular Diseases · doi:10.1016/j.numecd.2017.04.009 · Cited by 211 · see citing works
New mechanisms of metformin action: Focusing on mitochondria and the gut
Hur, K. Y., & Lee, M. (2015) · Journal of Diabetes Investigation · doi:10.1111/jdi.12328 · Cited by 161 · see citing works
Salomäki, H., Vähätalo, L. H., Laurila, K., Jäppinen, N. T., Penttinen, A.-M., Ailanen, L., Ilyasizadeh, J., Pesonen, U., & Koulu, M. (2013) · PLoS ONE · doi:10.1371/journal.pone.0056594 · Cited by 92 · see citing works
Packer, M. (2021) · Cardiovascular Research · doi:10.1093/cvr/cvaa064 · Cited by 86 · see citing works
Kanamori, H., Naruse, G., Yoshida, A., Minatoguchi, S., Watanabe, T., Kawaguchi, T., Yamada, Y., Mikami, A., Kawasaki, M., Takemura, G., et al. (2019) · Circulation: Heart Failure · doi:10.1161/circheartfailure.118.005418 · Cited by 84 · see citing works
Apoptosis and autophagy in polycystic kidney disease (PKD)
Nowak, K. L., & Edelstein, C. L. (2020) · Cellular Signalling · doi:10.1016/j.cellsig.2019.109518 · Cited by 71 · see citing works
AMPK is associated with the beneficial effects of antidiabetic agents on cardiovascular diseases
Lu, Q., Li, X., Liu, J., Sun, X., Rousselle, T., Ren, D., Tong, N., & Li, J. (2019) · Bioscience Reports · doi:10.1042/bsr20181995 · Cited by 69 · see citing works
Comprehensive autophagy evaluation in cardiac disease models
Kaludercic, N., Maiuri, M. C., Kaushik, S., Fernández, Á. F., de Bruijn, J., Castoldi, F., Chen, Y., Ito, J., Mukai, R., Murakawa, T., et al. (2020) · Cardiovascular Research · doi:10.1093/cvr/cvz233 · Cited by 64 · see citing works
Salomäki, H., Heinäniemi, M., Vähätalo, L. H., Ailanen, L., Eerola, K., Ruohonen, S. T., Pesonen, U., & Koulu, M. (2014) · PLoS ONE · doi:10.1371/journal.pone.0115778 · Cited by 63 · see citing works
Wang, G.-Y., Bi, Y.-G., Liu, X.-D., Zhao, Y., Han, J.-F., Wei, M., & Zhang, Q.-Y. (2017) · International Journal of Medical Sciences · doi:10.7150/ijms.19800 · Cited by 53 · see citing works
Wang, Q., Wu, S., Zhu, H., Ding, Y., Dai, X., Ouyang, C., Han, Y.-M., Xie, Z., & Zou, M.-H. (2017) · Autophagy · doi:10.1080/15548627.2016.1263776 · Cited by 45 · see citing works
Metformin and heart failure: never say never again
Papanas, N., Maltezos, E., & Mikhailidis, D. P. (2012) · Expert Opinion on Pharmacotherapy · doi:10.1517/14656566.2012.638283 · Cited by 39 · see citing works
Samuel, S. M., Ghosh, S., Majeed, Y., Arunachalam, G., Emara, M. M., Ding, H., & Triggle, C. R. (2017) · Biochemical Pharmacology · doi:10.1016/j.bcp.2017.03.001 · Cited by 37 · see citing works
Nutrient excess and autophagic deficiency: explaining metabolic diseases in obesity
van Niekerk, G., du Toit, A., Loos, B., & Engelbrecht, A.-M. (2018) · Metabolism · doi:10.1016/j.metabol.2017.12.007 · Cited by 34 · see citing works
Salomäki-Myftari, H., Vähätalo, L. H., Ailanen, L., Pietilä, S., Laiho, A., Hänninen, A., Pursiheimo, J.-P., Munukka, E., Rintala, A., Savontaus, E., et al. (2016) · PLOS ONE · doi:10.1371/journal.pone.0163805 · Cited by 33 · see citing works
NHX-5, an endosomal Na+/H+ exchanger, is associated with metformin action
Kim, J., Lee, H.-Y., Ahn, J., Hyun, M., Lee, I., Min, K.-J., & You, Y.-J. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.c116.744037 · Cited by 25 · see citing works
- Authors
- Xie, Z., Lau, K., Eby, B., Lozano, P., He, C., Pennington, B., Li, H., Rathi, S., Dong, Y., Tian, R., Kem, D., & Zou, M.-H.
- Affiliations
- University of Oklahoma Health Sciences Center (US)
- Oklahoma City VA Medical Center (US)
- University of Washington (US)
- Corresponding author
- Xie, Zhonglin
- ORCID
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2011-05-21
- Volume
- 60
- Issue
- 6
- Pages
- 1770-1778
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- PMC
- PMC3114402
- OpenAlex
- W2096317893
- Cited by
- 490
- References
- 49
- Citations by year
- 2026: 9 · 2025: 23 · 2024: 22 · 2023: 30 · 2022: 30 · 2021: 38 · 2020: 59 · 2019: 35 · 2018: 34 · 2017: 44 · 2016: 35 · 2015: 36 · 2014: 42 · 2013: 21 · 2012: 23
- FWCI
- 22.66
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Diabetes (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- American Diabetes Association
- American Heart Association
- Fraternal Order of Eagles
- University of Oklahoma
- Oklahoma Center for the Advancement of Science and Technology
- National Institutes of Health
- University of Oklahoma Health Sciences Center
- National Heart, Lung, and Blood Institute (R01HL105157, HL 079584, R01HL079584, HL-080499, HL096032, HL074399, R01HL074399, R01HL080499, HL-089920, R01HL110488, R01HL089920, R01HL096032)
- National Center for Research Resources (P20RR024215)
- Topics
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- metformin, cardiac autophagy, diabetic cardiomyopathy, AMPK, cardiomyocyte apoptosis, mitochondrial aggregation, polyubiquitinated proteins, cardiac dysfunction, heart failure
- MeSH terms
- Beclin-1, Animals, Autophagy, Echocardiography, Hypoglycemic Agents, Immunohistochemistry, Male, Metformin, Cardiomyopathies, Myocardium, Tuberous Sclerosis, Blotting, Western, Apoptosis, In Situ Nick-End Labeling, Myocytes, Cardiac, Microscopy, Electron, Transmission, Apoptosis Regulatory Proteins, Mice, AMP-Activated Protein Kinases
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
