Metformin Improves Mitochondrial Respiratory Activity through Activation of AMPK
Open accessAbstract
Impaired mitochondrial respiratory activity contributes to the development of insulin resistance in type 2 diabetes. Metformin, a first-line antidiabetic drug, functions mainly by improving patients' hyperglycemia and insulin resistance. However, its mechanism of action is still not well understood. We show here that pharmacological metformin concentration increases mitochondrial respiration, membrane potential, and ATP levels in hepatocytes and a clinically relevant metformin dose increases liver mitochondrial density and complex 1 activity along with improved hyperglycemia in high-fat- diet (HFD)-fed mice. Metformin, functioning through 5' AMP-activated protein kinase (AMPK), promotes mitochondrial fission to improve mitochondrial respiration and restore the mitochondrial life cycle. Furthermore, HFD-fed-mice with liver-specific knockout of AMPKα1/2 subunits exhibit higher blood glucose levels when treated with metformin. Our results demonstrate that activation of AMPK by metformin improves mitochondrial respiration and hyperglycemia in obesity. We also found that supra-pharmacological metformin concentrations reduce adenine nucleotides, resulting in the halt of mitochondrial respiration. These findings suggest a mechanism for metformin's anti-tumor effects.
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?
Metformin activates AMPK, improves mitochondrial function, decreases age-associated inflammation, and improves hyperglycaemia in people with obesity and prediabetes and in high-fat-diet-fed mice.
“Additionally, metformin, which is widely used to treat T2DM, activates AMPK, improves mitochondrial function, decreases age-associated inflammation and improves hyperglycaemia in people with obesity and prediabetes, as well as in HFD-fed mice238,239.”
From Mitochondrial and metabolic dysfunction in ageing and age-related diseases (2022) · cites this paper as [239]
In high-fat diet mice including AMPKα1/2 knockout mice treated with 50 mg/kg/day metformin in drinking water, complex 1 activity, mitochondria density and mitochondrial DNA were all increased via an AMPK-dependent mechanism.
“complex 1 activity, mitochondria density and mitochondrial DNA were all increased via an AMPK-dependent mechanism (138).”
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 [138]
Metformin may play an important role in quality-control regulation of mitochondria and shift cellular dynamics to a healthy population via mitophagy and eliminate damaged mitochondria.
“metformin may play an important role in the ‘quality-control’ regulation of mitochondria and shift the cellular dynamics to a healthy population via mitophagy and eliminate damaged mitochondria (138)”
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 [138]
If metformin can offset the decline in mitochondrial function, then this effect could contribute to enhancing both healthspan and lifespan.
“If metformin can offset the decline in mitochondrial function, as some studies suggest, then this effect could contribute to enhancing both healthspan and lifespan (138, 149, 150).”
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 [138]
Wang et al. reported that metformin protects complex 1 activity in hepatocytes but enhances mitochondria fission, thereby promoting healthy mitochondrial function via mitophagy.
“Wang et al. have reported that metformin protects complex 1 activity in a cell culture protocol in hepatocytes but enhances mitochondria fission, thereby promoting healthy mitochondrial function via mitophagy (138).”
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 [138]
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
Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin
(2002) · New England Journal of Medicine · doi:10.1056/nejmoa012512 · Cited by 19,011 · 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
AMPK: a nutrient and energy sensor that maintains energy homeostasis
Hardie, D. G., Ross, F. A., & Hawley, S. A. (2012) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3311 · Cited by 4,602 · see citing works
Mitochondrial Fission, Fusion, and Stress
Youle, R. J., & van der Bliek, A. M. (2012) · Science · doi:10.1126/science.1219855 · Cited by 3,674 · see citing works
Fission and selective fusion govern mitochondrial segregation and elimination by autophagy
Twig, G., Elorza, A., Molina, A. J. A., Mohamed, H., Wikstrom, J. D., Walzer, G., Stiles, L., Haigh, S. E., Katz, S., Las, G., et al. (2008) · The EMBO Journal · doi:10.1038/sj.emboj.7601963 · Cited by 3,082 · see citing works
Metformin and reduced risk of cancer in diabetic patients
Evans, J. M. M., Donnelly, L. A., Emslie-Smith, A. M., Alessi, D. R., & Morris, A. D. (2005) · BMJ · doi:10.1136/bmj.38415.708634.f7 · Cited by 2,388 · see citing works
Dysfunction of Mitochondria in Human Skeletal Muscle in Type 2 Diabetes
Kelley, D. E., He, J., Menshikova, E. V., & Ritov, V. B. (2002) · Diabetes · doi:10.2337/diabetes.51.10.2944 · Cited by 2,321 · see citing works
Mechanisms for Insulin Resistance: Common Threads and Missing Links
Samuel, V. T., & Shulman, G. I. (2012) · Cell · doi:10.1016/j.cell.2012.02.017 · Cited by 2,294 · see citing works
Impaired Mitochondrial Activity in the Insulin-Resistant Offspring of Patients with Type 2 Diabetes
Petersen, K. F., Dufour, S., Befroy, D., Garcia, R., & Shulman, G. I. (2004) · New England Journal of Medicine · doi:10.1056/nejmoa031314 · Cited by 2,193 · see citing works
OWEN, M. R., DORAN, E., & HALESTRAP, A. P. (2000) · Biochemical Journal · doi:10.1042/bj3480607 · Cited by 2,157 · see citing works
The Kinase LKB1 Mediates Glucose Homeostasis in Liver and Therapeutic Effects of Metformin
Shaw, R. J., Lamia, K. A., Vasquez, D., Koo, S.-H., Bardeesy, N., DePinho, R. A., Montminy, M., & Cantley, L. C. (2005) · Science · doi:10.1126/science.1120781 · Cited by 1,950 · see citing works
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 · see citing works
Proteasome and p97 mediate mitophagy and degradation of mitofusins induced by Parkin
Tanaka, A., Cleland, M. M., Xu, S., Narendra, D. P., Suen, D.-F., Karbowski, M., & Youle, R. J. (2010) · Journal of Cell Biology · doi:10.1083/jcb.201007013 · Cited by 1,369 · see citing works
Mitochondrial Dynamics in the Regulation of Nutrient Utilization and Energy Expenditure
Liesa, M., & Shirihai, O. S. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.03.002 · Cited by 1,341 · see citing works
Metformin suppresses gluconeogenesis by inhibiting mitochondrial glycerophosphate dehydrogenase
Madiraju, A. K., Erion, D. M., Rahimi, Y., Zhang, X.-M., Braddock, D. T., Albright, R. A., Prigaro, B. J., Wood, J. L., Bhanot, S., MacDonald, M. J., et al. (2014) · Nature · doi:10.1038/nature13270 · Cited by 1,284 · see citing works
Foretz, M., Hébrard, S., Leclerc, J., Zarrinpashneh, E., Soty, M., Mithieux, G., Sakamoto, K., Andreelli, F., & Viollet, B. (2010) · Journal of Clinical Investigation · doi:10.1172/jci40671 · Cited by 1,181 · see citing works
Dephosphorylation by calcineurin regulates translocation of Drp1 to mitochondria
Cereghetti, G. M., Stangherlin, A., de Brito, O. M., Chang, C. R., Blackstone, C., Bernardi, P., & Scorrano, L. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0808249105 · Cited by 1,129 · see citing works
Metformin inhibits mitochondrial complex I of cancer cells to reduce tumorigenesis
Wheaton, W. W., Weinberg, S. E., Hamanaka, R. B., Soberanes, S., Sullivan, L. B., Anso, E., Glasauer, A., Dufour, E., Mutlu, G. M., Budigner, G. S., et al. (2014) · eLife · doi:10.7554/elife.02242 · Cited by 1,105 · see citing works
AMP-activated protein kinase mediates mitochondrial fission in response to energy stress
Toyama, E. Q., Herzig, S., Courchet, J., Lewis, T. L., Losón, O. C., Hellberg, K., Young, N. P., Chen, H., Polleux, F., Chan, D. C., et al. (2016) · Science · doi:10.1126/science.aab4138 · Cited by 1,085 · see citing works
Mechanism by which metformin reduces glucose production in type 2 diabetes.
Hundal, R. S., Krssak, M., Dufour, S., Laurent, D., Lebon, V, Chandramouli, V, Inzucchi, S. E., Schumann, W. C., Petersen, K. F., Landau, B. R., et al. (2000) · Diabetes · doi:10.2337/diabetes.49.12.2063 · Cited by 1,052 · cited 1× · see citing works
“Metformin improves hyperglycemia in T2D mainly through suppression of liver glucose production and alleviation of insulin resistance (Hundal et al., 2000; Takashima et al., 2010).”
BackgroundRegulation of mitochondrial morphology through proteolytic cleavage of OPA1
Ishihara, N., Fujita, Y., Oka, T., & Mihara, K. (2006) · The EMBO Journal · doi:10.1038/sj.emboj.7601184 · Cited by 899 · see citing works
Fullerton, M. D., Galic, S., Marcinko, K., Sikkema, S., Pulinilkunnil, T., Chen, Z.-P., O'Neill, H. M., Ford, R. J., Palanivel, R., O'Brien, M., et al. (2013) · Nature Medicine · doi:10.1038/nm.3372 · Cited by 893 · see citing works
Deficiency of subsarcolemmal mitochondria in obesity and type 2 diabetes
Ritov, V. B., Menshikova, E. V., He, J., Ferrell, R. E., Goodpaster, B. H., & Kelley, D. E. (2005) · Diabetes · doi:10.2337/diabetes.54.1.8 · Cited by 887 · see citing works
Biguanides suppress hepatic glucagon signalling by decreasing production of cyclic AMP
Miller, R., Chu, Q., Xie, J., Foretz, M., Viollet, B., & Birnbaum, M. J. (2013) · Nature · doi:10.1038/nature11808 · Cited by 828 · see citing works
Morino, K. (2005) · Journal of Clinical Investigation · doi:10.1172/jci25151 · Cited by 811 · see citing works
Hawley, S. A., Gadalla, A. E., Olsen, G. S., & Hardie, D. G. (2002) · Diabetes · doi:10.2337/diabetes.51.8.2420 · Cited by 696 · see citing works
Effects of metformin and other biguanides on oxidative phosphorylation in mitochondria
Bridges, H. R., Jones, A. J. Y., Pollak, M. N., & Hirst, J. (2014) · Biochemical Journal · doi:10.1042/bj20140620 · Cited by 661 · see citing works
Antidiabetic Therapies Affect Risk of Pancreatic Cancer
Li, D., Yeung, S. J., Hassan, M. M., Konopleva, M., & Abbruzzese, J. L. (2009) · Gastroenterology · doi:10.1053/j.gastro.2009.04.013 · Cited by 584 · see citing works
Metformin Associated With Lower Cancer Mortality in Type 2 Diabetes
Landman, G. W. D., Kleefstra, N., van Hateren, K. J. J., Groenier, K. H., Gans, R. O. B., & Bilo, H. J. G. (2010) · Diabetes Care · doi:10.2337/dc09-1380 · Cited by 502 · see citing works
He, L., Sabet, A., Djedjos, S., Miller, R., Sun, X., Hussain, M. A., Radovick, S., & Wondisford, F. E. (2009) · Cell · doi:10.1016/j.cell.2009.03.016 · Cited by 479 · see citing works
Self-citationZang, M., Zuccollo, A., Hou, X., Nagata, D., Walsh, K., Herscovitz, H., Brecher, P. I., Ruderman, N. B., & Cohen, R. A. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m408149200 · Cited by 453 · see citing works
Insulin signaling meets mitochondria in metabolism
Cheng, Z., Tseng, Y. D., & White, M. F. (2010) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2010.06.005 · Cited by 449 · see citing works
Metformin Action: Concentrations Matter
He, L., & Wondisford, F. E. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.01.003 · Cited by 448 · see citing works
Accumulation of Metformin by Tissues of the Normal and Diabetic Mouse
Wilcock, C., & Bailey, C. J. (1994) · Xenobiotica · doi:10.3109/00498259409043220 · Cited by 418 · see citing works
Effective breast cancer combination therapy targeting BACH1 and mitochondrial metabolism
Lee, J., Yesilkanal, A. E., Wynne, J. P., Frankenberger, C. A., Liu, J., Yan, J., Elbaz, M., Rabe, D. C., Rustandy, F. D., Tiwari, P., et al. (2019) · Nature · doi:10.1038/s41586-019-1005-x · Cited by 380 · see citing works
Foxo1 integrates insulin signaling with mitochondrial function in the liver
Cheng, Z., Guo, S., Copps, K., Dong, X., Kollipara, R., Rodgers, J. T., Depinho, R. A., Puigserver, P., & White, M. F. (2009) · Nature Medicine · doi:10.1038/nm.2049 · Cited by 321 · see citing works
Self-citationYamada, T., Murata, D., Adachi, Y., Itoh, K., Kameoka, S., Igarashi, A., Kato, T., Araki, Y., Huganir, R. L., Dawson, T. M., et al. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.06.014 · Cited by 291 · see citing works
Self-citationDykens, J. A., Jamieson, J., Marroquin, L., Nadanaciva, S., Billis, P. A., & Will, Y. (2008) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2008.08.013 · Cited by 220 · see citing works
Metformin as an anti-cancer agent: actions and mechanisms targeting cancer stem cells
Saini, N., & Yang, X. (2017) · Acta Biochimica et Biophysica Sinica · doi:10.1093/abbs/gmx106 · Cited by 174 · see citing works
Cao, J., Meng, S., Chang, E., Beckwith-Fickas, K., Xiong, L., Cole, R. N., Radovick, S., Wondisford, F. E., & He, L. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.567271 · Cited by 169 · see citing works
Self-citationMeng, S., Cao, J., He, Q., Xiong, L., Chang, E., Radovick, S., Wondisford, F. E., & He, L. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.604421 · Cited by 146 · cited 2× · see citing works
“We reported that metformin activates AMPK by promoting the formation of the functional AMPKαβγ heterotrimeric complex and phosphorylation of the CREB-binding protein (He et al., 2009, 2014; Meng et al., 2015).”
BackgroundSelf-citationLee, Y. J., Jeschke, G. R., Roelants, F. M., Thorner, J. W., & Turk, B. E. (2012) · Molecular and Cellular Biology · doi:10.1128/mcb.00897-12 · Cited by 122 · see citing works
Role of KLF15 in Regulation of Hepatic Gluconeogenesis and Metformin Action
Takashima, M., Ogawa, W., Hayashi, K., Inoue, H., Kinoshita, S., Okamoto, Y., Sakaue, H., Wataoka, Y., Emi, A., Senga, Y., et al. (2010) · Diabetes · doi:10.2337/db09-1679 · Cited by 112 · see citing works
Endotoxemia-mediated activation of acetyltransferase P300 impairs insulin signaling in obesity
Cao, J., Peng, J., An, H., He, Q., Boronina, T. N., Guo, S., White, M. F., Cole, P. A., & He, L. (2017) · Nature Communications · doi:10.1038/s41467-017-00163-w · Cited by 88 · see citing works
Self-citationSubcellular Distribution of Metformin in Rat Liver
Wilcock, C., Wyre, N. D., & Bailey, C. J. (1991) · Journal of Pharmacy and Pharmacology · doi:10.1111/j.2042-7158.1991.tb03507.x · Cited by 86 · see citing works
Metformin-Treated Patients With Type 2 Diabetes Have Normal Mitochondrial Complex I Respiration
Larsen, S., Rabøl, R., Hansen, C. N., Madsbad, S., Helge, J. W., & Dela, F. (2012) · Diabetologia · doi:10.1007/s00125-011-2340-0 · Cited by 81 · see citing works
Guo, Y., Darshi, M., Ma, Y., Perkins, G. A., Shen, Z., Haushalter, K. J., Saito, R., Chen, A., Lee, Y. S., Patel, H. H., et al. (2013) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m113.027441 · Cited by 76 · see citing works
Effects of metformin on energy intake and satiety in obese children
Adeyemo, M. A., McDuffie, J. R., Kozlosky, M., Krakoff, J. A., Calis, K. A., Brady, S. M., & Yanovski, J. A. (2014) · Diabetes Obesity and Metabolism · doi:10.1111/dom.12426 · Cited by 61 · see citing works
Ghrelin and leptin levels in obese adolescents. Relationship with body fat and insulin resistance
Stylianou, C., Galli‐Τsinopoulou, A., Farmakiotis, D., Rousso, I., Karamouzis, M., Koliakos, G., & Nousia‐Arvanitakis, S. (2007) · HORMONES · doi:10.14310/horm.2002.1111025 · Cited by 55 · see citing works
Lee, H., & Yoon, Y. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.533299 · Cited by 51 · see citing works
Víctor, V. M., Rovira‐Llopis, S., Bañuls, C., Díaz‐Morales, N., Castelló, R., Falcón, R., Gómez, M., Rocha, M., & Hernández‐Mijares, A. (2015) · European Journal of Endocrinology · doi:10.1530/eje-15-0572 · Cited by 45 · see citing works
Activation of the cAMP-PKA pathway Antagonizes Metformin Suppression of Hepatic Glucose Production
He, L., Chang, E., Peng, J., An, H., McMillin, S. M., Radovick, S., Stratakis, C. A., & Wondisford, F. E. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m116.719666 · Cited by 38 · see citing works
Self-citationMetformin increases plasma ghrelin in Type 2 diabetes
Doogue, M. P., Begg, E. J., Moore, M. P., Lunt, H., Pemberton, C. J., & Zhang, M. (2009) · British Journal of Clinical Pharmacology · doi:10.1111/j.1365-2125.2009.03372.x · Cited by 34 · see citing works
Yamada, T., Ida, T., Yamaoka, Y., Ozawa, K., Takasan, H., & Honjo, I. (1975) · PubMed · Cited by 32 · see citing works
Potential biomarker of metformin action
He, L., Meng, S., Germain‐Lee, E. L., Radovick, S., & Wondisford, F. E. (2014) · Journal of Endocrinology · doi:10.1530/joe-14-0084 · Cited by 23 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Mitochondrial and metabolic dysfunction in ageing and age-related diseases
Amorim, J. A., Coppotelli, G., Rolo, A. P., Palmeira, C. M., Ross, J. M., & Sinclair, D. A. (2022) · Nature Reviews Endocrinology · doi:10.1038/s41574-021-00626-7 · Cited by 990 · see citing works
Panwar, V., Singh, A., Bhatt, M., Tonk, R. K., Azizov, S., Raza, A. S., Sengupta, S., Kumar, D., & Garg, M. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01608-z · Cited by 967 · see citing works
Role of Skeletal Muscle in Insulin Resistance and Glucose Uptake
Merz, K. E., & Thurmond, D. C. (2020) · Comprehensive Physiology · doi:10.1002/cphy.c190029 · Cited by 494 · see citing works
AMPK: restoring metabolic homeostasis over space and time
Trefts, E., & Shaw, R. J. (2021) · Molecular Cell · doi:10.1016/j.molcel.2021.08.015 · Cited by 463 · see citing works
Role of Skeletal Muscle in Insulin Resistance and Glucose Uptake
Merz, K. E., & Thurmond, D. C. (2020) · Comprehensive physiology · doi:10.1002/j.2040-4603.2020.tb00136.x · Cited by 283 · see citing works
Dahlén, A. D., Dashi, G., Maslov, I. O., Attwood, M. M., Jonsson, J., Trukhan, V., & Schiöth, H. B. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.807548 · Cited by 280 · see citing works
Mohammed, 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
Metformin: Is it a drug for all reasons and diseases?
Triggle, C. R., Mohammed, I., Bshesh, K., Marei, I., Ye, K., Ding, H., MacDonald, R. S., Hollenberg, M. D., & Hill, M. A. (2022) · Metabolism · doi:10.1016/j.metabol.2022.155223 · Cited by 281 · see citing works
Molecular Mechanisms of Adipogenesis: The Anti-adipogenic Role of AMP-Activated Protein Kinase
Ahmad, B., Serpell, C. J., Fong, I. L., & Wong, E. H. (2020) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2020.00076 · Cited by 253 · see citing works
Han, Y.-C., Tang, S.-Q., Liu, Y.-T., Li, A.-M., Zhan, M., Yang, M., Song, N., Zhang, W., Wu, X.-Q., Peng, C.-H., et al. (2021) · Cell Death & Disease · doi:10.1038/s41419-021-04184-8 · Cited by 257 · see citing works
Metformin and Systemic Metabolism
He, L. (2020) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2020.09.001 · Cited by 239 · see citing works
Self-citationTargeting OXPHOS and the electron transport chain in cancer; Molecular and therapeutic implications
Greene, J. P., Segaran, A., & Lord, S. (2022) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2022.02.002 · Cited by 212 · see citing works
Feng, J., Wang, X., Ye, X., Arés, I., López-Torres, B., Martínez, M., Martínez‐Larrañaga, M., Wang, X., Anadón, A., & Martínez, M. (2022) · Pharmacological Research · doi:10.1016/j.phrs.2022.106114 · Cited by 198 · see citing works
Metformin in aging and aging-related diseases: clinical applications and relevant mechanisms
Chen, S., Gan, D., Lin, S., Zhong, Y., Chen, M., Zou, X., Shao, Z., & Xiao, G. (2022) · Theranostics · doi:10.7150/thno.71360 · Cited by 197 · see citing works
The Metformin Mechanism on Gluconeogenesis and AMPK Activation: The Metabolite Perspective
Agius, L., Ford, B. E., & Chachra, S. S. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21093240 · Cited by 178 · see citing works
Peng, Y., Jin, H., Xue, Y.-H., Chen, Q., Yao, S., Du, M., & Liu, S. (2023) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2023.1206572 · Cited by 176 · see citing works
Chen, M., Wang, D., Li, M., He, Y., He, T., Chen, M., Hu, Y., Luo, Z. Y., & Cai, K. (2022) · ACS Nano · doi:10.1021/acsnano.2c07200 · Cited by 148 · see citing works
Intensive Care Unit-Acquired Weakness: Not Just Another Muscle Atrophying Condition
Lad, H., Saumur, T. M., Herridge, M. S., dos Santos, C. C., Mathur, S., Batt, J. A. E., & Gilbert, P. M. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21217840 · Cited by 136 · see citing works
Yao, W., Zhou, J., Tang, C., Zhang, J., Chen, Z., Li, Y., Gong, X., Qu, M., Zeng, Q., Jia, Y., et al. (2024) · ACS Nano · doi:10.1021/acsnano.4c06921 · Cited by 137 · see citing works
Mitochondrial complex I as a therapeutic target for Alzheimer's disease
Trushina, E. V., Trushin, S., & Hasan, M. F. (2021) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2021.11.003 · Cited by 130 · see citing works
En masse organoid phenotyping informs metabolic-associated genetic susceptibility to NASH
Kimura, M., Iguchi, T., Iwasawa, K., Dunn, A., Thompson, W. L., Yoneyama, Y., Chaturvedi, P., Zorn, A. M., Wintzinger, M., Quattrocelli, M., et al. (2022) · Cell · doi:10.1016/j.cell.2022.09.031 · Cited by 115 · see citing works
The Metabolic Basis of Immune Dysfunction Following Sepsis and Trauma
McBride, M. A., Owen, A. M., Stothers, C. L., Hernandez, A., Luan, L., Burelbach, K. R., Patil, T. K., Bohannon, J. K., Sherwood, E. R., & Patil, N. K. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.01043 · Cited by 116 · see citing works
Metformin-based nanomedicines for reprogramming tumor immune microenvironment
Liu, J., Li, X., Li, Y., Gong, Q., & Luo, K. (2024) · Theranostics · doi:10.7150/thno.104872 · Cited by 114 · see citing works
Marañón, A., Díaz-Pozo, P., Canet, F., Díaz‐Morales, N., Abad‐Jiménez, Z., López‐Domènech, S., Vezza, T., Apostolova, N., Morillas, C., Rocha, M., et al. (2022) · Redox Biology · doi:10.1016/j.redox.2022.102342 · Cited by 112 · see citing works
Legaki, A., Moustakas, I. I., Sikorska, M., Papadopoulos, G., Velliou, R.-I., & Chatzigeorgiou, A. (2022) · Current Obesity Reports · doi:10.1007/s13679-022-00473-1 · Cited by 108 · see citing works
Nutrient-sensing mTORC1 and AMPK pathways in chronic kidney diseases
Huynh, C. Q., Ryu, J., Lee, J., Inoki, A., & Inoki, K. (2022) · Nature Reviews Nephrology · doi:10.1038/s41581-022-00648-y · Cited by 104 · see citing works
LaMoia, T. E., Butrico, G. M., Kalpage, H. A., Goedeke, L., Hubbard, B. T., Vatner, D. F., Gaspar, R. C., Zhang, X., Cline, G. W., Nakahara, K., et al. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2122287119 · Cited by 103 · see citing works
Metformin: Experimental and Clinical Evidence for a Potential Role in Emphysema Treatment
Polverino, F., Wu, T. D., Rojas-Quintero, J., Wang, X., Mayo, J., Tomchaney, M., Tram, J., Packard, S., Zhang, D., Cleveland, K. H., et al. (2021) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.202012-4510oc · Cited by 100 · see citing works
Mitochondrial Dysfunction in Cardiovascular Diseases: Potential Targets for Treatment
Yang, J., Guo, Q., Feng, X., Liu, Y., & Zhou, Y. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.841523 · Cited by 102 · see citing works
Goel, S. K., Singh, R. P., Singh, V., Singh, H., Kumari, P., Chopra, H., Sharma, R., Nepovimová, E., Vališ, M., Kuča, K., et al. (2022) · Frontiers in Genetics · doi:10.3389/fgene.2022.1022739 · Cited by 112 · see citing works
Regulation and targeting of SREBP-1 in hepatocellular carcinoma
Su, F., & Koeberle, A. (2023) · Cancer and Metastasis Reviews · doi:10.1007/s10555-023-10156-5 · Cited by 100 · see citing works
The mitochondrial permeability transition: Nexus of aging, disease and longevity
Rottenberg, H., & Hoek, J. B. (2021) · Cells · doi:10.3390/cells10010079 · Cited by 94 · see citing works
“Spermidine induces autophagy by inducing the synthesis of the autophagy transcription factor TFEB [278] through the AMPK–mTORC1– ULK1 pathway [274].”
BackgroundInfluentialRole of mitochondrial quality control in the pathogenesis of nonalcoholic fatty liver disease
Li, R., Toan, S., & Zhou, H. (2020) · Aging · doi:10.18632/aging.102972 · Cited by 90 · see citing works
Targeting Mitochondria in Diabetes
Jakovljevic, N. K., Pavlović, K., Jotić, A., Lalic, K. S., Stoiljkovic, M. M., Lukić, L., Milicic, T. J., Macesic, M. V., Gajović, J. S., & Lalic, N. M. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22126642 · Cited by 90 · see citing works
Nam, B. Y., Jhee, J. H., Park, J., Kim, S., Kim, G., Park, J. T., Yoo, T., Kang, S., Yu, J., & Han, S. H. (2022) · Cell Death and Disease · doi:10.1038/s41419-021-04480-3 · Cited by 88 · see citing works
Metformin Repurposing for Parkinson Disease Therapy: Opportunities and Challenges
Agostini, F., Masato, A., Bubacco, L., & Bisaglia, M. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms23010398 · Cited by 90 · see citing works
Metformin in therapeutic applications in human diseases: its mechanism of action and clinical study
Du, Y., Zhu, Y., Zhou, Y., Ding, J., & Liu, J. (2022) · Molecular Biomedicine · doi:10.1186/s43556-022-00108-w · Cited by 82 · see citing works
mTOR signaling networks: mechanistic insights and translational frontiers in disease therapeutics
Zhang, H.-X., Xiao, X., Pan, Z.-R., & Dokudovskaya, S. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02493-4 · Cited by 90 · see citing works
Mitochondrial Metabolism in PDAC: From Better Knowledge to New Targeting Strategies
Reyes‐Castellanos, G., Masoud, R., & Carrier, A. (2020) · Biomedicines · doi:10.3390/biomedicines8080270 · Cited by 82 · see citing works
Szymczak-Pajor, I., Wenclewska, S., & Śliwińska, A. (2022) · Pharmaceuticals · doi:10.3390/ph15070810 · Cited by 81 · see citing works
Marek‐Iannucci, S., Ozdemir, A. B., Moreira, D., Gomez, A. C., Lane, M. E., Porritt, R. A., Lee, Y., Shimada, K., Abe, M., Stotland, A. B., et al. (2021) · JCI Insight · doi:10.1172/jci.insight.151981 · Cited by 77 · see citing works
Yan, Y., Li, M., Lin, J., Ji, Y., Wang, K., Yan, D., Shen, Y., Wang, W., Huang, Z., Jiang, H., et al. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.947387 · Cited by 81 · see citing works
Targeting of the tumor immune microenvironment by metformin
Wu, Z., Zhang, C., & Najafi, M. (2021) · Journal of Cell Communication and Signaling · doi:10.1007/s12079-021-00648-w · Cited by 75 · see citing works
Cheng, L., Deepak, R. N. V. K., Wang, G., Meng, Z., Tao, L., Xie, M., Chi, W., Zhang, Y., Yang, M., Liao, Y., et al. (2023) · Hepatology · doi:10.1097/hep.0000000000000314 · Cited by 74 · see citing works
Self-citationZhang, Y., Liu, W., Zhong, Y., Li, Q., Wu, M., Yang, L., Liu, X., & Zou, L. (2021) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2021/1806344 · Cited by 73 · see citing works
The Mechanism of Action of Biguanides: New Answers to a Complex Question
Magno, L. D., Pastena, F. D., Bordone, R., Coni, S., & Canettieri, G. (2022) · Cancers · doi:10.3390/cancers14133220 · Cited by 75 · see citing works
Balan, A. I., Halațiu, V.-B., & Scridon, A. (2024) · Antioxidants · doi:10.3390/antiox13010117 · Cited by 69 · see citing works
Yu, T., Wang, L., Zhang, L., & Deuster, P. A. (2023) · Antioxidants · doi:10.3390/antiox12061163 · Cited by 71 · see citing works
Mitochondrial disorders leading to Alzheimer’s disease—perspectives of diagnosis and treatment
Pszczołowska, M., Walczak, K., Miśków, W., Mroziak, M., Chojdak-Łukasiewicz, J., & Leszek, J. (2024) · GeroScience · doi:10.1007/s11357-024-01118-y · Cited by 62 · see citing works
Diabetes: a tipping point in neurodegenerative diseases
Santiago, J. A., Karthikeyan, M., Lackey, M., Villavicencio, D., & Potashkin, J. A. (2023) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2023.09.005 · Cited by 64 · see citing works
Katila, N., Bhurtel, S., Park, P., & Choi, D. (2021) · Neurochemistry International · doi:10.1016/j.neuint.2021.105120 · Cited by 59 · see citing works
The Role of Mitochondria in the Chemoresistance of Pancreatic Cancer Cells
Fu, Y., Ricciardiello, F., Yang, G., Qiu, J., Huang, H., Xiao, J., Cao, Z., Zhao, F., Liu, Y., Luo, W., et al. (2021) · Cells · doi:10.3390/cells10030497 · Cited by 57 · see citing works
Effects of imeglimin on mitochondrial function, AMPK activity, and gene expression in hepatocytes
Hozumi, K., Sugawara, K., Ishihara, T., Ishihara, N., & Ogawa, W. (2023) · Scientific Reports · doi:10.1038/s41598-023-27689-y · Cited by 62 · see citing works
The Anti-Aging Mechanism of Metformin: From Molecular Insights to Clinical Applications
Zhang, T., Li-jun, Z., Makarczyk, M. J., Feng, P., & Zhang, J. (2025) · Molecules · doi:10.3390/molecules30040816 · Cited by 58 · see citing works
Song, F., Lee, W. D., Marmo, T., Ji, X., Song, C., Liao, X., Seeley, R. A., Yao, L., Liu, H., & Long, F. (2023) · eLife · doi:10.7554/elife.85714 · Cited by 55 · see citing works
STAT3/LKB1 controls metastatic prostate cancer by regulating mTORC1/CREB pathway
Pěnčík, J., Philippe, C., Schlederer, M., Atas, E., Pecoraro, M., Grund‐Gröschke, S., Li, W., Tracz, A., Heidegger, I. M., Lagger, S., et al. (2023) · Molecular Cancer · doi:10.1186/s12943-023-01825-8 · Cited by 52 · see citing works
Magno, L. D., Manni, S., Pastena, F. D., Coni, S., Macone, A., Cairoli, S., Sambucci, M., Infante, P., Moretti, M., Petroni, M., et al. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.01.024 · Cited by 53 · see citing works
García-Puga, M., Saenz‐Antoñanzas, A., Fernández‐Torrón, R., de Munaín, A. L., & Matheu, A. (2020) · Aging · doi:10.18632/aging.103022 · Cited by 50 · see citing works
Why the endothelium? The endothelium as a target to reduce diabetes-associated vascular disease
Triggle, C. R., Ding, H., Marei, I., Anderson, T. J., & Hollenberg, M. D. (2020) · Canadian Journal of Physiology and Pharmacology · doi:10.1139/cjpp-2019-0677 · Cited by 49 · see citing works
Promising use of metformin in treating neurological disorders: biomarker-guided therapies
Loan, A., Syal, C., Lui, M., He, L., & Wang, J. (2023) · Neural Regeneration Research · doi:10.4103/1673-5374.385286 · Cited by 49 · see citing works
Self-citationYang, G., Yang, J., Diao, Z., Long, J., Shu, Z., Liu, C. J., & Wan, W. (2025) · Science Advances · doi:10.1126/sciadv.adw3834 · Cited by 50 · see citing works
The AMPK Pathway: Molecular Rejuvenation of Metabolism and Mitochondria
Malik, N., & Shaw, R. J. (2025) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-120420-094431 · Cited by 52 · see citing works
Takashima, M., Nakamura, K., Kiyohara, T., Wakisaka, Y., Hidaka, M., Takaki, H., Yamanaka, K., Shibahara, T., Wakisaka, M., Ago, T., et al. (2022) · Communications Biology · doi:10.1038/s42003-022-03605-4 · Cited by 44 · see citing works
Paul, S. C., Saha, D., & Binukumar, B. K. (2021) · Molecular Neurobiology · doi:10.1007/s12035-021-02365-2 · Cited by 43 · see citing works
Host-directed therapy for tuberculosis
Tian, N., Chu, H., Li, Q., Sun, H., Zhang, J., Chu, N., & Sun, Z. (2025) · European journal of medical research · doi:10.1186/s40001-025-02443-4 · Cited by 43 · see citing works
Insulin resistance in Alzheimer’s disease: The genetics and metabolomics links
Amin, A. M., Mostafa, H. M. A., & Khojah, H. M. J. (2022) · Clinica Chimica Acta · doi:10.1016/j.cca.2022.12.016 · Cited by 43 · see citing works
Yang, L., Wang, D., Zhang, Z., Jiang, Y., & Liu, Y. (2022) · Phytomedicine · doi:10.1016/j.phymed.2022.153950 · Cited by 42 · see citing works
Metabolomic Approaches to Investigate the Effect of Metformin: An Overview
Kim, H. W. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms221910275 · Cited by 41 · see citing works
Xu, Q., Zhang, J., Lu, Y., & Wu, L. Y. (2024) · iScience · doi:10.1016/j.isci.2024.108783 · Cited by 40 · see citing works
Mitochondria as a promising target for developing novel agents for treating Alzheimer's disease
Shevtsova, E. F., Maltsev, A. V., Vinogradova, D. V., Shevtsov, P. N., & Бачурин, С. О. (2020) · Medicinal Research Reviews · doi:10.1002/med.21715 · Cited by 41 · see citing works
Biphasic effect of metformin on human cardiac energetics
Emelyanova, L. V., Bai, X., Yan, Y., Bosnjak, Z. J., Kress, D. C., Warner, C., Kroboth, S. L., Rudic, T., Kaushik, S., Stoeckl, E. M., et al. (2020) · Translational research · doi:10.1016/j.trsl.2020.10.002 · Cited by 40 · see citing works
Angebault, C., Panel, M., Lacôte, M., Rieusset, J., Lacampagne, A., & Fauconnier, J. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.609493 · Cited by 40 · see citing works
Meta-Assessment of Metformin Absorption and Disposition Pharmacokinetics in Nine Species
Jeong, Y., & Jusko, W. J. (2021) · Pharmaceuticals · doi:10.3390/ph14060545 · Cited by 41 · see citing works
Mitochondria-Targeted Antioxidant Therapeutics for Traumatic Brain Injury
Modi, H. R., Musyaju, S., Ratcliffe, M., Shear, D. A., Scultetus, A. H., & Pandya, J. D. (2024) · Antioxidants · doi:10.3390/antiox13030303 · Cited by 42 · see citing works
PGC-1α-Targeted Therapeutic Approaches to Enhance Muscle Recovery in Aging
Petrocelli, J. J., & Drummond, M. J. (2020) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph17228650 · Cited by 39 · see citing works
Tang, C., Xu, J. P., Ye, H.-Y., & Wang, X. (2021) · Experimental and Therapeutic Medicine · doi:10.3892/etm.2021.10013 · Cited by 39 · see citing works
Mahmoud, M. F., Abdelaal, S., Mohammed, H. O., El-Shazly, A. M., Daoud, R., Raey, M. A. E., & Sobeh, M. (2021) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2021.112085 · Cited by 39 · see citing works
Miguel, V., Rey, C., Tituaña, J., Sirera, B., Alcalde‐Estévez, E., Herrero, J. I., Ranz, I., Fernández, L., Castillo, C., Sevilla, L. F. V., et al. (2023) · Redox Biology · doi:10.1016/j.redox.2023.102957 · Cited by 38 · see citing works
Xu, L., Ma, F., Huang, J., Leung, K. L. F., Qin, C., Lu, W. W., Guo, X., & Tang, B. (2021) · Biomacromolecules · doi:10.1021/acs.biomac.0c01488 · Cited by 38 · see citing works
Self-citationIn situ observation of mitochondrial biogenesis as the early event of apoptosis
Shao, C., Zhou, X., Miao, Y., Wang, P., Zhang, Q., & Huang, Q. (2021) · iScience · doi:10.1016/j.isci.2021.103038 · Cited by 38 · see citing works
T-cell senescence: A crucial player in autoimmune diseases
Lu, Y., Ruan, Y., Pan, H., Rui, K., Liu, Q., Wang, S., & Cui, D. (2022) · Clinical Immunology · doi:10.1016/j.clim.2022.109202 · Cited by 37 · see citing works
Chen, A., Kristiansen, C. K., Hong, Y., Kianian, A., Fang, E. F., Sullivan, G. J., Wang, J., Li, X., Bindoff, L. A., & Liang, K. X. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.737304 · Cited by 36 · see citing works
Zhu, L., Liu, J., Qiu, M.-J., Chen, J., Liang, Q. D., Peng, G., & Zou, Z. (2022) · Biomaterials · doi:10.1016/j.biomaterials.2022.121711 · Cited by 37 · see citing works
Metformin and the Liver: Unlocking the Full Therapeutic Potential
Perazza, F., Leoni, L., Colosimo, S., Musio, A., Bocedi, G., D’Avino, M., Agnelli, G., Nicastri, A., Rossetti, C., Sacilotto, F., et al. (2024) · Metabolites · doi:10.3390/metabo14040186 · Cited by 38 · see citing works
Disrupting metformin adaptation of liver cancer cells by targeting the TOMM34/ATP5B axis
Jin, P., Jiang, J., Zhou, L., Huang, Z., Qin, S., Chen, H., Peng, L., Zhang, Z., Li, B., Luo, M., et al. (2022) · EMBO Molecular Medicine · doi:10.15252/emmm.202216082 · Cited by 35 · see citing works
Moonira, T., Chachra, S. S., Ford, B. E., Marín, S., Alshawi, A., Adam-Primus, N. S., Arden, C., Al‐Oanzi, Z. H., Foretz, M., Viollet, B., et al. (2020) · Journal of Biological Chemistry · doi:10.1074/jbc.ra120.012533 · Cited by 34 · see citing works
Palee, S., Higgins, L., Leech, T., Chattipakorn, S. C., & Chattipakorn, N. (2020) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2020.110604 · Cited by 36 · see citing works
RetractedNocquet, L., Juin, P. P., & Souazé, F. (2020) · Cancers · doi:10.3390/cancers12103017 · Cited by 34 · see citing works
Sun, Y., Zhao, Z., Qiao, Q., Li, S., Yu, W., Guan, X., Schneider, A., Weir, M. D., Xu, H. H. K., Zhang, K., et al. (2023) · Dental Materials · doi:10.1016/j.dental.2023.07.008 · Cited by 34 · see citing works
Nuclear VCP drives colorectal cancer progression by promoting fatty acid oxidation
Huang, Y., Wang, F., Lin, X., Li, Q., Lu, Y., Zhang, J., Shen, X. H., Tan, J., Qin, Z., Chen, J., et al. (2023) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2221653120 · Cited by 33 · see citing works
Glycation by glyoxal leads to profound changes in the behavior of dermal fibroblasts
Guillon, C., Ferraro, S., Clément, S., Bouschbacher, M., Sigaudo‐Roussel, D., & Bonod‐Bidaud, C. (2021) · BMJ Open Diabetes Research & Care · doi:10.1136/bmjdrc-2020-002091 · Cited by 33 · see citing works
The role of metformin as a treatment for neuropsychiatric illness
Dodd, S., Sominsky, L., Siskind, D. J., Bortolasci, C. C., Carvalho, A. F., Maes, M. H. J., Walker, A. J., Walder, K. R., Yung, A. R., Williams, L. J., et al. (2022) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2022.09.002 · Cited by 33 · see citing works
Nandwani, A., Rathore, S., & Datta, M. (2023) · Redox Biology · doi:10.1016/j.redox.2023.102989 · Cited by 33 · see citing works
Borges, C. M., Fujihara, C. K., Malheiros, D. M. A. C., Ávila, V. F., Formigari, G. P., & de Faria, J. B. L. (2020) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00539.2019 · Cited by 32 · see citing works
Lerner, A., Kewada, D., Ahmed, A., Hardy, K., Christian, M., & Franks, S. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms22010243 · Cited by 33 · see citing works
Peng, J., Qin, C., Ramatchandirin, B., Pearah, A., Guo, S., Hussain, M. A., Yu, L., Wondisford, F. E., & He, L. (2022) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2022.102283 · Cited by 32 · see citing works
Self-citationMetformin: From diabetes to cancer to prolongation of life
Sirtori, C. R., Castiglione, S., & Pavanello, C. (2024) · Pharmacological Research · doi:10.1016/j.phrs.2024.107367 · Cited by 33 · see citing works
Therapeutic effect of metformin in the treatment of endometrial cancer (Review)
Mu, N., Xu, T., Gao, M., Dong, M., Tang, Q., Li, H., Wang, G., Li, Z., Wang, W., Yang, Y., et al. (2020) · Oncology Letters · doi:10.3892/ol.2020.12017 · Cited by 31 · see citing works
Repas, J., Zupin, M., Vodlan, M., Veranič, P., Gole, B., Potočnik, U., & Pavlin, M. (2022) · Cancers · doi:10.3390/cancers14051343 · Cited by 32 · see citing works
He, L., Wu, X., Zhan, F., Li, X., & Wu, J. (2023) · Placenta · doi:10.1016/j.placenta.2023.10.003 · Cited by 30 · see citing works
Self-citation
- Authors
- Wang, Y., An, H., Liu, T., Qin, C., Sesaki, H., Guo, S., Radovick, S., Hussain, M., Maheshwari, A., Wondisford, F. E., O’Rourke, B., & He, L.
- Affiliations
- Johns Hopkins University (US)
- Texas A&M University (US)
- Rutgers, The State University of New Jersey (US)
- University of Michigan (US)
- Corresponding author
- He, Ling
- ORCID
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2019-11
- Volume
- 29
- Issue
- 6
- Pages
- 1511-1523.e5
- ISSN
- 2211-1247 (ISSN-L)
- PMC
- PMC6866677
- OpenAlex
- W2985421076
- Cited by
- 432
- References
- 55
- Citations by year
- 2026: 53 · 2025: 70 · 2024: 63 · 2023: 62 · 2022: 82 · 2021: 62 · 2020: 38 · 2014: 1
- FWCI
- 15.05
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion, cc-by-nc-nd)
- PubMed Central (acceptedVersion, cc-by-nc-nd)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health
- 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 › Epidemiology › Autophagy in Disease and Therapy
- Keywords
- metformin, AMPK, mitochondrial respiration, mitochondrial fission, mitochondrial dynamics, insulin resistance, type 2 diabetes, hyperglycemia, high-fat diet, hepatocytes, liver mitochondria, complex I, mitochondrial membrane potential, ATP production, obesity, anti-tumor effect, adenine nucleotides
- MeSH terms
- AMP-Activated Protein Kinase Kinases, Adenine Nucleotides, Animals, Blood Glucose, Hyperglycemia, Hypoglycemic Agents, Insulin Resistance, Liver, Metformin, Mice, Inbred C57BL, Mitochondria, Liver, Protein Kinases, Cell Respiration, Hepatocytes, Electron Transport Complex I, Mice, AMP-Activated Protein Kinases, Gene Knockout Techniques, Diet, High-Fat, Mitochondrial Dynamics
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
