Metformin reduces liver glucose production by inhibition of fructose-1-6-bisphosphatase
Open accessAbstract
Metformin is a first-line drug for the treatment of individuals with type 2 diabetes, yet its precise mechanism of action remains unclear. Metformin exerts its antihyperglycemic action primarily through lowering hepatic glucose production (HGP). This suppression is thought to be mediated through inhibition of mitochondrial respiratory complex I, and thus elevation of 5′-adenosine monophosphate (AMP) levels and the activation of AMP-activated protein kinase (AMPK), though this proposition has been challenged given results in mice lacking hepatic AMPK. Here we report that the AMP-inhibited enzyme fructose-1,6-bisphosphatase-1 (FBP1), a rate-controlling enzyme in gluconeogenesis, functions as a major contributor to the therapeutic action of metformin. We identified a point mutation in FBP1 that renders it insensitive to AMP while sparing regulation by fructose-2,6-bisphosphate (F-2,6-P2), and knock-in (KI) of this mutant in mice significantly reduces their response to metformin treatment. We observe this during a metformin tolerance test and in a metformin-euglycemic clamp that we have developed. The antihyperglycemic effect of metformin in high-fat diet–fed diabetic FBP1-KI mice was also significantly blunted compared to wild-type controls. Collectively, we show a new mechanism of action for metformin and provide further evidence that molecular targeting of FBP1 can have antihyperglycemic effects. The antidiabetic action of metformin raises heptocyte intracellular AMP levels, causing allosteric inhibition of fructose-1,6-bisphosphatase and thus reductions in gluconeogenesis.
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Metformin suppresses hepatic glucose production via AMP-induced inhibition of fructose-1,6-bisphosphatase-1.
“metformin’s suppression of hepatic glucose production is shown to be the result of AMP-induced inhibition of fructose-1,6-bisphosphatase-1, a rate-controlling enzyme in gluconeogenesis”
From Benefits of Metformin in Attenuating the Hallmarks of Aging (2020) · cites this paper as Hunter et al. 2018
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Cites
Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT Method
Livak, K. J., & Schmittgen, T. D. (2001) · Methods · doi:10.1006/meth.2001.1262 · Cited by 180,860 · see citing works
(1975) · Journal of AOAC INTERNATIONAL · doi:10.1093/jaoac/58.5.1085 · Cited by 20,078 · 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
Mutation of the mouse klotho gene leads to a syndrome resembling ageing
Kuro-o, M., Matsumura, Y., Aizawa, H., Kawaguchi, H., Suga, T., Utsugi, T., Ohyama, Y., Kurabayashi, M., Kaname, T., Kume, E., et al. (1997) · Nature · doi:10.1038/36285 · Cited by 3,837 · see citing works
Watterson, K. R., Bestow, D., Gallagher, J. R., Hamilton, D. L., Ashford, F. B., Meakin, P. J., & Ashford, M. L. J. (2012) · Neurosignals · doi:10.1159/000334144 · Cited by 3,395 · 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
Srere, P. A. (1969) · Methods in Enzymology · doi:10.1016/0076-6879(69)13005-0 · Cited by 2,005 · 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
Wu, H., Esteve, E., Tremaroli, V., Khan, M. T., Caesar, R., Mannerås-Holm, L., Ståhlman, M., Olsson, L. M., Serino, M., Planas-Fèlix, M., et al. (2017) · Nature Medicine · doi:10.1038/nm.4345 · Cited by 1,632 · 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
Clinical pharmacokinetics of metformin
Graham, G. G., Punt, J., Arora, M., Day, R. O., Doogue, M. P., Duong, J. K., Furlong, T. J., Greenfield, J. R., Greenup, L. C., Kirkpatrick, C. M., et al. (2011) · Clinical Pharmacokinetics · doi:10.2165/11534750-000000000-00000 · Cited by 1,318 · 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
Thomas, J. A., Schlender, K. K., & Larner, J. (1968) · Analytical Biochemistry · doi:10.1016/0003-2697(68)90127-9 · Cited by 1,198 · 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
Self-citationCool, B. L., Zinker, B. A., Chiou, W. J. H., Kifle, L., Cao, N., Perham, M., Dickinson, R., Adler, A. L., Gagné, G. D., Iyengar, R., et al. (2006) · Cell Metabolism · doi:10.1016/j.cmet.2006.05.005 · Cited by 932 · 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
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
Use of Cells Expressing γ Subunit Variants to Identify Diverse Mechanisms of AMPK Activation
Hawley, S. A., Ross, F. A., Chevtzoff, C., Green, K. A., Evans, A., Fogarty, S., Towler, M. C., Brown, L. J., Ogunbayo, O. A., Evans, A. M., et al. (2010) · Cell Metabolism · doi:10.1016/j.cmet.2010.04.001 · Cited by 773 · 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
A Kinetic Study of Pyrophosphate: Fructose‐6‐Phosphate Phosphotransferase from Potato Tubers
SCHAFTINGEN, E. V., Lederer, B., Bartrons, R., & Hers, H. G. (1982) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1982.tb07039.x · Cited by 652 · see citing works
Drug excretion mediated by a new prototype of polyspecific transporter
Gründemann, D., Gorboulev, V., Gambaryan, S. P., Veyhl, M., & Koepsell, H. (1994) · Nature · doi:10.1038/372549a0 · Cited by 642 · see citing works
Enzymatic analysis; a practical guide
(1993) · General Pharmacology The Vascular System · doi:10.1016/0306-3623(93)90404-l · Cited by 522 · see citing works
Contributions of gluconeogenesis to glucose production in the fasted state
Landau, B. R., Wahren, J., Chandramouli, V, Schumann, W. C., Ekberg, K., & Kalhan, S. C. (1996) · Journal of Clinical Investigation · doi:10.1172/jci118803 · Cited by 487 · see citing works
Molecular mechanism of action of metformin: old or new insights?
Rena, G., Pearson, E. R., & Sakamoto, K. (2013) · Diabetologia · doi:10.1007/s00125-013-2991-0 · Cited by 479 · see citing works
Self-citationDetermination of confidence intervals of metabolic fluxes estimated from stable isotope measurements
Antoniewicz, M. R., Kelleher, J. K., & Stephanopoulos, G. N. (2006) · Metabolic Engineering · doi:10.1016/j.ymben.2006.01.004 · Cited by 451 · see citing works
Satapati, S., Sunny, N. E., Kucejova, B., Fu, X., He, T. T., Méndez-Lucas, A., Shelton, J. M., Perales, J. C., Browning, J. D., & Burgess, S. C. (2012) · Journal of Lipid Research · doi:10.1194/jlr.m023382 · Cited by 407 · see citing works
Metformin Activates a Duodenal Ampk-Dependent Pathway to Lower Hepatic Glucose Production in Rats
Duca, F. A., Côté, C. D., Rasmussen, B. A., Zadeh-Tahmasebi, M., Rutter, G. A., Filippi, B. M., & Lam, T. K. T. (2015) · Nature Medicine · doi:10.1038/nm.3787 · Cited by 402 · see citing works
Radioactive method for the assay of glycogen phosphorylases
Gilboe, D. P., Larson, K., & Nuttall, F. Q. (1972) · Analytical Biochemistry · doi:10.1016/0003-2697(72)90274-6 · Cited by 402 · see citing works
INCA: a computational platform for isotopically non-stationary metabolic flux analysis
Young, J. D. (2014) · Bioinformatics · doi:10.1093/bioinformatics/btu015 · Cited by 398 · see citing works
The Stimulation of Liver Phosphorylase b by AMP, Fluoride and Sulfate
Stalmans, W., & Hers, H. G. (1975) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1975.tb04144.x · Cited by 308 · see citing works
Passonneau, J. V., & Lowry, O. H. (1993) · Humana Press eBooks · doi:10.1007/978-1-60327-407-4 · Cited by 300 · see citing works
Niclosamide ethanolamine–induced mild mitochondrial uncoupling improves diabetic symptoms in mice
Tao, H., Zhang, Y., Zeng, X., Shulman, G. I., & Jin, S. (2014) · Nature Medicine · doi:10.1038/nm.3699 · Cited by 288 · see citing works
Bailey, C. J., Wilcock, C., & Scarpello, J. H. B. (2008) · Diabetologia · doi:10.1007/s00125-008-1053-5 · Cited by 275 · see citing works
Bleasby, K., Castle, J. C., Roberts, C. J., Cheng, C., Bailey, W. J., Sina, J. F., Kulkarni, A., Hafey, M., Evers, R., Johnson, J. M., et al. (2006) · Xenobiotica · doi:10.1080/00498250600861751 · Cited by 269 · see citing works
Christensen, M. M. H., Brasch‐Andersen, C., Gréen, H., Nielsen, F., Damkier, P., Beck‐Nielsen, H., & Brøsen, K. (2011) · Pharmacogenetics and Genomics · doi:10.1097/fpc.0b013e32834c0010 · Cited by 258 · see citing works
The specificities of small molecule inhibitors of the TGFß and BMP pathways
Vogt, J., Traynor, R., & Sapkota, G. P. (2011) · Cellular Signalling · doi:10.1016/j.cellsig.2011.06.019 · Cited by 256 · see citing works
Metformin Activates AMP Kinase through Inhibition of AMP Deaminase
Ouyang, J., Parakhia, R. A., & Ochs, R. S. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.121806 · Cited by 246 · see citing works
Chen, L., Shu, Y., Liang, X., Chen, E. C., Yee, S. W., Zur, A. A., Li, S., Xu, L., Keshari, K. R., Lin, M. J., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1314939111 · Cited by 234 · see citing works
Inhibition by AICA Riboside of Gluconeogenesis in Isolated Rat Hepatocytes
Vincent, M., Marangos, P. J., Gruber, H. E., & Berghe, G. (1991) · Diabetes · doi:10.2337/diab.40.10.1259 · Cited by 218 · see citing works
Saheki, S., Takeda, A., & Shimazu, T. (1985) · Analytical Biochemistry · doi:10.1016/0003-2697(85)90229-5 · Cited by 217 · see citing works
Rp, F., Seitz, H. J., Tarnowski, W., Thiemann, V., & Weiß, C. (1972) · Archives of Biochemistry and Biophysics · doi:10.1016/0003-9861(72)90170-1 · Cited by 209 · see citing works
Smiley, K. L., Berry, A. J., & Suelter, C. H. (1967) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)95990-9 · Cited by 201 · see citing works
Davidson, A. L., & Arion, W. J. (1987) · Archives of Biochemistry and Biophysics · doi:10.1016/0003-9861(87)90648-5 · Cited by 198 · see citing works
Allosteric Regulation of Glycogen Synthase Controls Glycogen Synthesis in Muscle
Bouskila, M., Hunter, R. W., Ibrahim, A. F. M., Delattre, L., Peggie, M., van Diepen, J. A., Voshol, P. J., Jensen, J., & Sakamoto, K. (2010) · Cell Metabolism · doi:10.1016/j.cmet.2010.10.006 · Cited by 196 · see citing works
Self-citationChomczyński, P., & Rymaszewski, M. (2006) · BioTechniques · doi:10.2144/000112149 · Cited by 192 · see citing works
Guigas, B., Bertrand, L., Taleux, N., Foretz, M., Wiernsperger, N. F., Vertommen, D., Andréelli, F., Viollet, B., & Hue, L. (2006) · Diabetes · doi:10.2337/diabetes.55.04.06.db05-1178 · Cited by 179 · see citing works
Samuel, V. T., Beddow, S. A., Iwasaki, T., Zhang, X., Chu, X., Still, C. D., Gerhard, G. S., & Shulman, G. I. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0812547106 · Cited by 176 · see citing works
Blair, J. B., Cimbala, M. A., Foster, J. L., & Morgan, R. A. (1976) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)33408-7 · Cited by 170 · see citing works
Erion, M. D., van Poelje, P. D., Dang, Q., Kasibhatla, S. R., Potter, S. C., Reddy, M. R., Reddy, K. R., Jiang, T., & Lipscomb, W. N. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0502983102 · Cited by 162 · see citing works
The LKB1-salt-inducible kinase pathway functions as a key gluconeogenic suppressor in the liver
Patel, K., Foretz, M., Marion, A., Campbell, D. G., Gourlay, R., Boudaba, N., Tournier, E., Titchenell, P. M., Peggie, M. W., Deák, M., et al. (2014) · Nature Communications · doi:10.1038/ncomms5535 · Cited by 162 · see citing works
Self-citationHyperinsulinemic-euglycemic Clamps in Conscious, Unrestrained Mice
Ayala, J. E., Bracy, D. P., Malabanan, C. M., James, F. D., Ansari, T., Fueger, P. T., McGuinness, O. P., & Wasserman, D. H. (2011) · Journal of Visualized Experiments · doi:10.3791/3188 · Cited by 157 · see citing works
Self-citationRyll, T., & Wagner, R. (1991) · Journal of Chromatography B Biomedical Sciences and Applications · doi:10.1016/0378-4347(91)80202-n · Cited by 155 · see citing works
Argaud, D., Roth, H., Wiernsperger, N. F., & Leverve, X. M. (1993) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1993.tb17886.x · Cited by 151 · see citing works
Gormsen, L. C., Sundelin, E. I. O., Jensen, J., Vendelbo, M. H., Jakobsen, S., Munk, O. L., Christensen, M. M. H., Brøsen, K., Frøkiær, J., & Jessen, N. (2016) · Journal of Nuclear Medicine · doi:10.2967/jnumed.116.177774 · Cited by 145 · see citing works
Self-citationInactivation of phosphofructokinase by glucagon in rat hepatocytes.
Castaño, J. G., Nieto, A., & Felíu, J. E. (1979) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)50447-6 · Cited by 137 · see citing works
Measuring Deuterium Enrichment of Glucose Hydrogen Atoms by Gas Chromatography/Mass Spectrometry
Antoniewicz, M. R., Kelleher, J. K., & Stephanopoulos, G. N. (2011) · Analytical Chemistry · doi:10.1021/ac200012p · Cited by 137 · see citing works
Stepensky, D., Friedman, M., Raz, I., & Hoffman, A. (2002) · Drug Metabolism and Disposition · doi:10.1124/dmd.30.8.861 · Cited by 135 · see citing works
Kjøbsted, R., Treebak, J. T., Fentz, J., Lantier, L., Viollet, B., Birk, J. B., Schjerling, P., Björnholm, M., Zierath, J. R., & Wojtaszewski, J. F. P. (2014) · Diabetes · doi:10.2337/db14-1402 · Cited by 135 · see citing works
Self-citationTerada, T., Masuda, S., Asaka, J., Tsuda, M., Katsura, T., & Inui, K. (2006) · Pharmaceutical Research · doi:10.1007/s11095-006-9016-3 · Cited by 130 · see citing works
Mechanism of Action of Compound-13: An α1-Selective Small Molecule Activator of AMPK
Hunter, R. W., Foretz, M., Bultot, L., Fullerton, M. D., Deák, M., Ross, F. A., Hawley, S. A., Shpiro, N., Viollet, B., Barron, D., et al. (2014) · Chemistry & Biology · doi:10.1016/j.chembiol.2014.05.014 · Cited by 125 · see citing works
Self-citationRapid determination of metformin in human plasma using ion-pair HPLC
Zarghi, A., Foroutan, S. M., Shafaati, A., & Khoddam, A. (2003) · Journal of Pharmaceutical and Biomedical Analysis · doi:10.1016/s0731-7085(02)00608-8 · Cited by 119 · see citing works
Petrescu, I., Bojan, O., Saied, M., Bârzu, O., Schmidt, F. H., & Kühnle, H. F. (1979) · Analytical Biochemistry · doi:10.1016/0003-2697(79)90582-7 · Cited by 113 · see citing works
Hepatic fructose-1,6-diphosphatase deficiency
Pagliara, A. S., Karl, I. E., Keating, J., Brown, B. I., & KIPNIS, D. M. (1972) · Journal of Clinical Investigation · doi:10.1172/jci107018 · Cited by 112 · 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
Dang, Q., Kasibhatla, S. R., Reddy, K. R., Jiang, T., Reddy, M. R., Potter, S. C., Fujitaki, J. M., van Poelje, P. D., Huang, J., Lipscomb, W. N., et al. (2007) · Journal of the American Chemical Society · doi:10.1021/ja074871l · Cited by 100 · see citing works
Hypoglycaemic effect of AICAriboside in mice
Vincent, M. F., Erion, M. D., Gruber, H. E., & den Berghe, G. V. (1996) · Diabetologia · doi:10.1007/bf02658500 · Cited by 93 · see citing works
Jensen, J., Sundelin, E. I. O., Jakobsen, S., Gormsen, L. C., Munk, O. L., Frøkiær, J., & Jessen, N. (2016) · Diabetes · doi:10.2337/db16-0032 · Cited by 90 · see citing works
Self-citationLalau, J., Lemaire‐Hurtel, A., & Lacroix, C. (2011) · Clinical Drug Investigation · doi:10.2165/11588310-000000000-00000 · Cited by 87 · see citing works
Gidh‐Jain, M., Zhang, Y., van Poelje, P. D., Liang, J. Y., Huang, S., Kim, J., Elliott, J. T., Erion, M. D., Pilkis, S. J., & El‐Maghrabi, M. R. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)47047-0 · Cited by 82 · see citing works
Hasenour, C. M., Wall, M. L., Ridley, D. E., Hughey, C. C., James, F. D., Wasserman, D. H., & Young, J. D. (2015) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00003.2015 · Cited by 80 · see citing works
Self-citationHasenour, C. M., Ridley, D. E., Hughey, C. C., James, F. D., Donahue, E. P., Shearer, J., Viollet, B., Foretz, M., & Wasserman, D. H. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.528232 · Cited by 69 · see citing works
Self-citationZhang, Y., Xie, Z., Zhou, G., Zhang, H., Lu, J., & Zhang, W. J. (2010) · Endocrinology · doi:10.1210/en.2009-1185 · Cited by 36 · see citing works
Bosselaar, M., Smits, P., van Loon, L. J. C., & Tack, C. J. (2010) · The Journal of Clinical Pharmacology · doi:10.1177/0091270010382912 · Cited by 30 · see citing works
Yoshida, T., Okuno, A., Tanaka, J., Takahashi, K., Nakashima, R., Kanda, S., Ogawa, J., Hagisawa, Y., & Fujiwara, T. (2009) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2009.09.003 · Cited by 29 · see citing works
Purification and Properties of Mouse Liver Fructose 1, 6-Bisphosphatase
Tashima, Y., MIZUNUMA, H., & Hasegawa, M. (1979) · The Journal of Biochemistry · doi:10.1093/oxfordjournals.jbchem.a132603 · Cited by 25 · see citing works
Vincent, M. F., Bontemps, F., & den Berghe, G. V. (1996) · Biochemical Pharmacology · doi:10.1016/0006-2952(96)00413-3 · Cited by 25 · see citing works
Nelson, S. W., Choe, J., Honzatko, R. B., & Fromm, H. J. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m000473200 · Cited by 25 · see citing works
Jakobsen, S., Busk, M., Jensen, J., Munk, O. L., Zois, N. E., Alstrup, A. K. O., Jessen, N., & Frøkiær, J. (2016) · Journal of Nuclear Medicine · doi:10.2967/jnumed.115.169292 · Cited by 25 · see citing works
Self-citationDiscovery of fructose-1,6-bisphosphatase inhibitors for the treatment of type 2 diabetes.
van Poelje, P. D., Dang, Q., & Erion, M. D. (2007) · PubMed · Cited by 20 · see citing works
Giroux, E. L., Williams, M., & Kantrowitz, E. R. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)31708-3 · Cited by 17 · see citing works
McCarty, M. F. (1999) · Medical Hypotheses · doi:10.1054/mehy.1997.0597 · Cited by 16 · see citing works
Racker, E. (1965) · Elsevier eBooks · doi:10.1016/b978-0-12-395630-9.50031-1 · Cited by 12 · see citing works
Enzymatic assay of hemoglobin in tissue homogenates with chlorpromazine
Nakamura, K., Maeda, H., & Kawaguchi, H. (1987) · Analytical Biochemistry · doi:10.1016/0003-2697(87)90196-5 · Cited by 8 · see citing works
Han, P. F., Han, G., McBay, H. C., & Johnson, J. D. (1982) · Analytical Biochemistry · doi:10.1016/0003-2697(82)90280-9 · Cited by 6 · see citing works
Flagged first, then by citations
1 of the 86 references couldn’t be matched to a known paper.
Research works printed but not linked: 1
- [20]Faupel RP Seitz HJ Tarnowski W Thiemann V Weiss C The problem of tissue sampling from experimental animals with respect to freezing technique, anoxia, stress and narcosis. A new method for sampling rat liver tissue and the physiological values of glycolytic intermediates and related compounds Arch Biochem Biophys 1972 148 509 522 5019872
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Steinberg, G. R., & Hardie, D. G. (2022) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-022-00547-x · Cited by 1,023 · see citing works
Cellular and Molecular Mechanisms of Metformin Action
LaMoia, T. E., & Shulman, G. I. (2021) · Endocrine Reviews · doi:10.1210/endrev/bnaa023 · Cited by 791 · see citing works
Benefits of Metformin in Attenuating the Hallmarks of Aging
Kulkarni, A. S., Gubbi, S., & Barzilai, N. (2020) · Cell Metabolism · doi:10.1016/j.cmet.2020.04.001 · Cited by 766 · see citing works
Metformin: update on mechanisms of action and repurposing potential
Foretz, M., Guigas, B., & Viollet, B. (2023) · Nature Reviews Endocrinology · doi:10.1038/s41574-023-00833-4 · Cited by 744 · see citing works
Understanding the glucoregulatory mechanisms of metformin in type 2 diabetes mellitus
Foretz, M., Guigas, B., & Viollet, B. (2019) · Nature Reviews Endocrinology · doi:10.1038/s41574-019-0242-2 · Cited by 686 · see citing works
Low-dose metformin targets the lysosomal AMPK pathway through PEN2
Ma, T., Tian, X., Zhang, B., Li, M., Wang, Y., Yang, C., Wu, J., Wei, X., Qu, Q., Yu, Y., et al. (2022) · Nature · doi:10.1038/s41586-022-04431-8 · Cited by 644 · see citing works
Metformin and Its Benefits for Various Diseases
Lv, Z., & Guo, Y. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.00191 · Cited by 544 · see citing works
Gestational diabetes mellitus - A metabolic and reproductive disorder
Choudhury, A. A., & Rajeswari, V. D. (2021) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2021.112183 · Cited by 447 · see citing works
Unraveling the regulation of hepatic gluconeogenesis
Zhang, X., Yang, S., Chen, J., & Su, Z. (2019) · Frontiers in Endocrinology · doi:10.3389/fendo.2018.00802 · Cited by 314 · see citing works
Day, E. A., Ford, R. J., Smith, B. K., Mohammadi-Shemirani, P., Morrow, M. R., Gutgesell, R. M., Lu, R., Raphenya, A. R., Kabiri, M., McArthur, A. G., et al. (2019) · Nature Metabolism · doi:10.1038/s42255-019-0146-4 · Cited by 307 · see citing works
Role of mitochondria in the mechanism(s) of action of metformin
Vial, G., Detaille, D., & Guigas, B. (2019) · Frontiers in Endocrinology · doi:10.3389/fendo.2019.00294 · Cited by 303 · 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
Metformin as Anti-Aging Therapy: Is It for Everyone?
Soukas, A. A., Hao, H., & Wu, L. (2019) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2019.07.015 · Cited by 260 · see citing works
Metformin: A Review of Potential Mechanism and Therapeutic Utility Beyond Diabetes
Dutta, S., Shah, R., Singhal, S., Dutta, S. B., Bansal, S., Sinha, S., & Haque, M. (2023) · Drug Design Development and Therapy · doi:10.2147/dddt.s409373 · Cited by 284 · see citing works
Metformin and Systemic Metabolism
He, L. (2020) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2020.09.001 · Cited by 242 · see citing works
Serine Catabolism Feeds NADH when Respiration Is Impaired
Yang, L., García‐Cañaveras, J. C., Chen, Z., Wang, L., Liang, L., Jang, C., Mayr, J. A., Zhang, Z., Ghergurovich, J. M., Zhan, L., et al. (2020) · Cell Metabolism · doi:10.1016/j.cmet.2020.02.017 · Cited by 213 · 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
AICAr, a Widely Used AMPK Activator with Important AMPK-Independent Effects: A Systematic Review
Višnjić, D., Lalić, H., Dembitz, V., Tomić, B., & Smoljo, T. (2021) · Cells · doi:10.3390/cells10051095 · Cited by 164 · see citing works
Pharmacotherapy of type 2 diabetes: An update and future directions
DeMarsilis, A. J., Reddy, N., Boutari, C., Filippaios, A., Sternthal, E., Katsiki, N., & Mantzoros, C. S. (2022) · Metabolism · doi:10.1016/j.metabol.2022.155332 · Cited by 161 · see citing works
The strange case of AMPK and cancer: Dr Jekyll or Mr Hyde?
Vara‐Ciruelos, D., Russell, F. M., & Hardie, D. G. (2019) · Open Biology · doi:10.1098/rsob.190099 · Cited by 136 · see citing works
Anticancer mechanisms of metformin: A review of the current evidence
Zhao, B., Luo, J., Yu, T., Zhou, L., Lv, H., & Shang, P. (2020) · Life Sciences · doi:10.1016/j.lfs.2020.117717 · Cited by 124 · see citing works
Li, L., Yang, L., Fan, Z., Xue, W., Shen, Z., Yuan, Y., Sun, X., Wang, D., Lian, J., Wang, L., et al. (2020) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-020-0152-8 · Cited by 110 · see citing works
A review of phenformin, metformin, and imeglimin
Yendapally, R., Sikazwe, D., Kim, S. S., Ramsinghani, S., Fraser‐Spears, R., Witte, A. P., & Viola, B. L. (2020) · Drug Development Research · doi:10.1002/ddr.21636 · Cited by 111 · 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
Yang, Y., Wen, R., Yang, N., Zhang, T., & Liu, C. (2023) · Molecular Medicine · doi:10.1186/s10020-023-00684-9 · Cited by 102 · see citing works
Non-Small-Cell Lung Cancer Signaling Pathways, Metabolism, and PD-1/PD-L1 Antibodies
Santarpía, M., Aguilar, A., CHAIB-OUKADOUR, I., Cardona, A. F., Fancelli, S., Laguía, F., Bracht, J. W. P., Cao, P., Molina‐Vila, M. Á., Karachaliou, N., et al. (2020) · Cancers · doi:10.3390/cancers12061475 · Cited by 100 · see citing works
The aldolase inhibitor aldometanib mimics glucose starvation to activate lysosomal AMPK
Zhang, C., Li, M., Wang, Y., Li, X., Zong, Y., Long, S., Zhang, M., Feng, J.-W., Wei, X., Liu, Y., et al. (2022) · Nature Metabolism · doi:10.1038/s42255-022-00640-7 · Cited by 99 · see citing works
AMPK and the Endocrine Control of Metabolism
Townsend, L. K., & Steinberg, G. R. (2023) · Endocrine Reviews · doi:10.1210/endrev/bnad012 · Cited by 107 · see citing works
Integrative analysis of the plasma proteome and polygenic risk of cardiometabolic diseases
Ritchie, S. C., Lambert, S. A., Arnold, M., Teo, S. M., Lim, S. I., Šćepanović, P., Marten, J., Zahid, S., Chaffin, M. D., Liu, Y., et al. (2021) · Nature Metabolism · doi:10.1038/s42255-021-00478-5 · Cited by 94 · see citing works
Scaricamazza, S., Salvatori, I., Giacovazzo, G., Loeffler, J., René, F., Rosina, M., Quessada, C., Proietti, D., Heil, C., Rossi, S., et al. (2020) · iScience · doi:10.1016/j.isci.2020.101087 · Cited by 95 · see citing works
Effects of Metformin in Heart Failure: From Pathophysiological Rationale to Clinical Evidence
Salvatore, T., Galiero, R., Caturano, A., Vetrano, E., Rinaldi, L., Coviello, F., Martino, A. D., Albanese, G., Marfella, R., Sardu, C., et al. (2021) · Biomolecules · doi:10.3390/biom11121834 · Cited by 97 · see citing works
Alshawi, A., & Agius, L. (2018) · Journal of Biological Chemistry · doi:10.1074/jbc.ra118.006670 · Cited by 85 · 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
Morita, H., Kano, C., Ishii, C., Kagata, N., Ishikawa, T., Hirayama, A., Uchiyama, Y., Hara, S., Nakamura, T., & Fukuda, S. (2023) · Science Advances · doi:10.1126/sciadv.add2120 · Cited by 82 · see citing works
Li, N., Zhou, T. G., & Fei, E. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23158281 · Cited by 83 · see citing works
Szymczak-Pajor, I., Wenclewska, S., & Śliwińska, A. (2022) · Pharmaceuticals · doi:10.3390/ph15070810 · Cited by 81 · see citing works
Metformin acts in the gut and induces gut-liver crosstalk
Tobar, N., Rocha, G. Z., Santos, A., Guadagnini, D., Assalin, H. B., de Camargo, J. A., Gonçalves, A. E. S. S., Pallis, F. R., Oliveira, A. G., Rocco, S. A., et al. (2023) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2211933120 · Cited by 78 · see citing works
Collodet, C., Foretz, M., Deák, M., Bultot, L., Métairon, S., Viollet, B., Lefebvre, G., Raymond, F., Parisi, A., Civiletto, G., et al. (2019) · The FASEB Journal · doi:10.1096/fj.201900841r · Cited by 74 · see citing works
Self-citationYang, W., Zhu, D., Gan, S., Dong, X., Su, J.-P., Li, W., Jiang, H., Zhao, W., Yao, M., Song, W., et al. (2022) · Nature Medicine · doi:10.1038/s41591-022-01803-5 · 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
Metformin: A Candidate Drug for Renal Diseases
Corremans, R., Vervaet, B. A., D’Haese, P. C., Neven, E., & Verhulst, A. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms20010042 · Cited by 69 · see citing works
Larsen, A. H., Jessen, N., Nørrelund, H., Tolbod, L., Harms, H., Feddersen, S., Nielsen, F., Brøsen, K., Hansson, N. H., Frøkiær, J., et al. (2019) · European Journal of Heart Failure · doi:10.1002/ejhf.1656 · Cited by 54 · see citing works
Self-citationThe metabolic sensor AMPK: Twelve enzymes in one
Smiles, W. J., Ovens, A. J., Oakhill, J. S., & Kofler, B. (2024) · Molecular Metabolism · doi:10.1016/j.molmet.2024.102042 · Cited by 65 · see citing works
The role of AMPK in metabolism and its influence on DNA damage repair
Szewczuk, M., Boguszewska, K., Kaźmierczak-Barańska, J., & Karwowski, B. T. (2020) · Molecular Biology Reports · doi:10.1007/s11033-020-05900-x · Cited by 66 · see citing works
Du, F., Liu, M., Wang, J., Hu, L., Zeng, D., Zhou, S., Zhang, L., Wang, M., Xu, X., Li, C., et al. (2023) · Metabolism · doi:10.1016/j.metabol.2023.155398 · Cited by 63 · see citing works
Hu, D., Guo, Y., Wu, R., Shao, T., Long, J., Yu, B., Wang, H. H., Luo, Y., Lu, H., Zhang, J., et al. (2021) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.120.315708 · Cited by 61 · see citing works
Metformin targets mitochondrial complex I to lower blood glucose levels
Reczek, C. R., Chakrabarty, R. P., D’Alessandro, K. B., Sebo, Z. L., Grant, R. A., Gao, P., Budinger, G. R. S., & Chandel, N. S. (2024) · Science Advances · doi:10.1126/sciadv.ads5466 · Cited by 62 · see citing works
FBP1 controls liver cancer evolution from senescent MASH hepatocytes
Gu, L., Zhu, Y., Nandi, S. P., Lee, M., Watari, K., Bareng, B., Ohira, M., Liu, Y., Sakane, S., Carlessi, R., et al. (2025) · Nature · doi:10.1038/s41586-024-08317-9 · Cited by 60 · see citing works
Pharmacology of metformin – An update
Glossmann, H. H., & Lutz, O. M. D. (2019) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2019.172782 · Cited by 61 · see citing works
Morita, Y., Nogami, M., Sakaguchi, K., Okada, Y., Hirota, Y., Sugawara, K., Tamori, Y., Zeng, F., Murakami, T., & Ogawa, W. (2020) · Diabetes Care · doi:10.2337/dc20-0093 · Cited by 59 · see citing works
Metformin and Vascular Diseases: A Focused Review on Smooth Muscle Cell Function
Deng, M., Su, D., Xu, S., Little, P. J., Feng, X., Tang, L., & Shen, A. (2020) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.00635 · Cited by 58 · see citing works
Zhang, Y., Wang, H., & Xiao, H. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22095016 · 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
Metformin: From Diabetes to Cancer—Unveiling Molecular Mechanisms and Therapeutic Strategies
Amengual-Cladera, E., Morla-Barcelo, P. M., Morán-Costoya, A., Valle, A., Pons, D. G., Sastre‐Serra, J., Roca, P., & Nadal‐Serrano, M. (2024) · Biology · doi:10.3390/biology13050302 · Cited by 67 · see citing works
AMP-Activated Protein Kinase: Do We Need Activators or Inhibitors to Treat or Prevent Cancer?
Russell, F. M., & Hardie, D. G. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms22010186 · Cited by 57 · see citing works
Drug Repurposing for Cancer Treatment: A Comprehensive Review
Khzem, A. H. A., Gomaa, M. S., Alturki, M. S., Tawfeeq, N., Sarafroz, M., Alonaizi, S. M., Faran, A. A., Alrumaihi, L. A., AlAnsari, F., & Alghamdi, A. A. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms252212441 · Cited by 55 · see citing works
Metformin and its therapeutic applications in autoimmune inflammatory rheumatic disease
Kim, J., Choe, J., & Park, S. (2021) · The Korean Journal of Internal Medicine · doi:10.3904/kjim.2021.363 · Cited by 56 · see citing works
AMPK as a mediator of tissue preservation: time for a shift in dogma?
Langer, H. T., Rohm, M., Goncalves, M. D., & Sylow, L. (2024) · Nature Reviews Endocrinology · doi:10.1038/s41574-024-00992-y · Cited by 51 · see citing works
Linking bioenergetic function of mitochondria to tissue-specific molecular fingerprints
Kappler, L., Hoene, M., Hu, C., von Toerne, C., Li, J., Bleher, D., Hoffmann, C., Böhm, A., Kollipara, L., Zischka, H., et al. (2019) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00088.2019 · Cited by 50 · see citing works
Investigation of the specificity and mechanism of action of the ULK1/AMPK inhibitor SBI-0206965
Ahwazi, D., Neopane, K., Markby, G. R., Kopietz, F., Ovens, A. J., Dall, M., Hassing, A. S., Gräsle, P., Alshuweishi, Y., Treebak, J. T., et al. (2021) · Biochemical Journal · doi:10.1042/bcj20210284 · Cited by 51 · see citing works
Self-citationHe, M., Ye, M., Li, B., Wu, T., Lu, C., Liu, P., Li, H., Zhou, X., Wang, Y., Liang, T., et al. (2022) · Sensors and Actuators B Chemical · doi:10.1016/j.snb.2022.131868 · Cited by 47 · see citing works
Fructose-1,6-bisphosphatase 1 dephosphorylates IκBα and suppresses colorectal tumorigenesis
Zhu, W., Chu, H., Zhang, Y., Luo, T., Yu, H. T., Zhu, H., Liu, Y., Gao, H., Zhao, Y., Li, Q., et al. (2023) · Cell Research · doi:10.1038/s41422-022-00773-0 · Cited by 50 · see citing works
Chen, Y., Shen, X., Ma, T., Yu, X., Kwok, L., Li, Y., Sun, Z., Li, D., & Zhang, H. (2023) · mSystems · doi:10.1128/msystems.01300-22 · Cited by 48 · see citing works
Lipotoxicity as a therapeutic target in obesity and diabetic cardiomyopathy
Nakamura, M. (2024) · Journal of Pharmacy & Pharmaceutical Sciences · doi:10.3389/jpps.2024.12568 · Cited by 50 · see citing works
AMPK mediates energetic stress‐induced liver GDF15
Townsend, L. K., Weber, A. J., Day, E. A., Shamshoum, H., Shaw, S. J., Perry, C. G. R., Kemp, B. E., Steinberg, G. R., & Wright, D. C. (2020) · The FASEB Journal · doi:10.1096/fj.202000954r · Cited by 46 · see citing works
MASLD development: From molecular pathogenesis toward therapeutic strategies
Yang, Z., Zhao, J., Xie, K., Tang, C., Gan, C., & Gao, J. (2025) · Chinese Medical Journal · doi:10.1097/cm9.0000000000003629 · Cited by 47 · see citing works
Fructose 1,6- bis phosphatase: getting the message across
Timson, D. J. (2019) · Bioscience Reports · doi:10.1042/bsr20190124 · Cited by 45 · see citing works
Liao, K. L., Deng, S., Xu, L., Pan, W., Yang, S., Zheng, F., Wu, X., Hu, H., Liu, Z., Luo, J., et al. (2020) · Cancer Research · doi:10.1158/0008-5472.can-19-2060 · Cited by 43 · see citing works
A human antibody against pathologic IAPP aggregates protects beta cells in type 2 diabetes models
Wirth, F., Heitz, F. D., Seeger, C., Combaluzier, I., Breu, K., Denroche, H. C., Thévenet, J., Osto, M., Arosio, P., Kerr-Conte, J. A., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-41986-0 · Cited by 44 · see citing works
Gu, L., Zhu, Y., Watari, K., Lee, M., Liu, J., Perez, S., Thai, M., Mayfield, J. E., Zhang, B., Rocha, K. C. E., et al. (2023) · Cell Metabolism · doi:10.1016/j.cmet.2023.03.021 · Cited by 43 · see citing works
Matsukawa, T., Yagi, T., Uchida, T., Sakai, M., Mitsushima, M., Naganuma, T., Yano, H., Inaba, Y., Inoue, H., Yanagida, K., et al. (2023) · JCI Insight · doi:10.1172/jci.insight.161282 · Cited by 42 · see citing works
Meng, J., Han, J., Wang, X., Wu, T., Zhang, H., An, H., Qin, L., Sun, Y., Zhong, W., Yang, C., et al. (2023) · Pharmacological Research · doi:10.1016/j.phrs.2023.106661 · Cited by 41 · see citing works
Zhao, X., Zhang, X., Pei, J., Liu, Y., Niu, W., & Sun, H. (2023) · Diabetologia · doi:10.1007/s00125-023-05985-6 · Cited by 39 · see citing works
100 years of the Warburg effect: a historical perspective
Hardie, D. G. (2022) · Endocrine Related Cancer · doi:10.1530/erc-22-0173 · Cited by 43 · see citing works
Effects of High Dietary Carbohydrate and Lipid Intake on the Lifespan of C. elegans
Franco-Juárez, B., Gómez‐Manzo, S., Hernández‐Ochoa, B., Cárdenas‐Rodríguez, N., Arreguín‐Espinosa, R., de la Cruz, V. P., & Ortega-Cuéllar, D. (2021) · Cells · doi:10.3390/cells10092359 · Cited by 38 · see citing works
AMPK inhibits liver gluconeogenesis: fact or fiction?
Johanns, M., Hue, L., & Rider, M. H. (2023) · Biochemical Journal · doi:10.1042/bcj20220582 · Cited by 42 · see citing works
Updated Understanding of the Crosstalk Between Glucose/Insulin and Cholesterol Metabolism
Xiao, X., Luo, Y., & Peng, D. (2022) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2022.879355 · Cited by 36 · see citing works
Metformin Intervention—A Panacea for Cancer Treatment?
Buczyńska, A., Sidorkiewicz, I., Kretowski, A. J., Zbucka-Krętowska, M., & Adamska, A. (2022) · Cancers · doi:10.3390/cancers14051336 · Cited by 36 · see citing works
Huang, Y., Xu, Y., Song, R., Ni, S., Liu, J., Xu, Y., Ren, Y., Rao, L., Wang, Y., Wei, L., et al. (2020) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.0c00699 · Cited by 33 · see citing works
Zheng, J., Xu, M., Yang, Q., Hu, C., Walker, V. M., Lu, J., Wang, J., Liu, R., Xu, Y., Wang, T., et al. (2023) · EBioMedicine · doi:10.1016/j.ebiom.2023.104803 · Cited by 34 · see citing works
The direct targets of metformin in diabetes and beyond
Yao, L., Wang, L., Zhang, R., Soukas, A. A., & Wu, L. (2024) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2024.07.017 · Cited by 39 · 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
Hepatic Glucose Output Inhibition by Mexican Plants Used in the Treatment of Type 2 Diabetes
Mata-Torres, G., Adolfo Andrade-cetto, A., Espinoza-Hernández, F. A., & Cárdenas-Vázquez, R. (2020) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.00215 · Cited by 34 · see citing works
Molecules Isolated from Mexican Hypoglycemic Plants: A Review
Escandón–Rivera, S., Mata, R., & Adolfo Andrade-cetto, A. (2020) · Molecules · doi:10.3390/molecules25184145 · Cited by 34 · see citing works
Sam68 promotes hepatic gluconeogenesis via CRTC2
Qiao, A., Zhou, J., Xu, S., Ma, W., Boriboun, C., Kim, T., Yan, B., Deng, J., Liu, Y., Zhang, E. W., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-23624-9 · Cited by 34 · see citing works
Water‐Soluble Gold(III)–Metformin Complex Alters Mitochondrial Bioenergetics in Breast Cancer Cells
Kim, J. H., Ofori, S., Mertens, R. T., Parkin, S., & Awuah, S. G. (2021) · ChemMedChem · doi:10.1002/cmdc.202100233 · Cited by 34 · see citing works
Research progress on AMPK in the pathogenesis and treatment of MASLD
Jiang, F., Li, M., Yao, T., Yi, X., & Gao, H.-N. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1558041 · Cited by 45 · see citing works
MCCREIGHT, L. J., Mari, A., Coppin, L., Jackson, N., Umpleby, A. M., & Pearson, E. R. (2019) · Diabetologia · doi:10.1007/s00125-019-05042-1 · Cited by 33 · see citing works
Xiao, Y., Li, K., Bian, J., Liu, H., Zhai, X., El-Omar, E. M., Han, L., Gong, L., & Wang, M. (2022) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.202100863 · Cited by 32 · see citing works
Breast Cancer Subtypes Underlying EMT-Mediated Catabolic Metabolism
Cho, E. S., Kim, N. H., Yun, J. S., Cho, S. B., Kim, H. S., & Yook, J. I. (2020) · Cells · doi:10.3390/cells9092064 · Cited by 31 · see citing works
The Potential Therapeutic Role of Metformin in Diabetic and Non-Diabetic Bone Impairment
Mu, W., Liang, G., Feng, Y., Jiang, Y., & Qu, F. (2022) · Pharmaceuticals · doi:10.3390/ph15101274 · Cited by 30 · see citing works
Lü, C., Ren, C., Yang, T., Sun, Y., Qiao, P., Wang, D., Lv, S., & Yu, Z. (2020) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-19-0842 · Cited by 31 · see citing works
Nyambuya, T. M., Dludla, P. V., Mxinwa, V., Mokgalaboni, K., Ngcobo, S. R., Tiano, L., & Nkambule, B. B. (2020) · Life Sciences · doi:10.1016/j.lfs.2020.117854 · Cited by 30 · see citing works
Rhein, P., Desjardins, E. M., Rong, P., Ahwazi, D., Bonhoure, N., Stolte, J., Santos, M. D., Ovens, A. J., Ehrlich, A. M., Sanchez-Garcia, J. L., et al. (2021) · Molecular Metabolism · doi:10.1016/j.molmet.2021.101228 · Cited by 30 · see citing works
Self-citationDu, Y., Zhu, J., Guo, Z., Wang, Z., Wang, Y., Hu, M., Zhang, L., Yang, Y., Wang, J., Huang, Y., et al. (2024) · Expert Review of Clinical Pharmacology · doi:10.1080/17512433.2024.2306223 · Cited by 30 · see citing works
Of mice and men: Is there a future for metformin in the treatment of hepatic steatosis?
Green, C., Marjot, T., Tomlinson, J., & Hodson, L. (2018) · Diabetes Obesity and Metabolism · doi:10.1111/dom.13592 · Cited by 29 · see citing works
Li, P., Li, K., Yuan, W., Xu, Y., Li, P., Wu, R., Han, J., Yin, Z., Lu, L., & Gao, Y. (2023) · Theranostics · doi:10.7150/thno.84645 · Cited by 28 · see citing works
Shi, Y., Zhang, Y., Luo, H., Xu, F., Gao, J.-M., Shi, J., & Gong, Q. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.828473 · Cited by 28 · see citing works
Chemical genetic screen identifies Gapex-5/GAPVD1 and STBD1 as novel AMPK substrates
Ducommun, S., Deák, M., Zeigerer, A., Göransson, O., Seitz, S., Collodet, C., Madsen, A. B., Jensen, T. E., Viollet, B., Foretz, M., et al. (2019) · Cellular Signalling · doi:10.1016/j.cellsig.2019.02.001 · Cited by 28 · see citing works
Self-citationKristensen, J. M., Lillelund, C., Kjøbsted, R., Birk, J. B., Andersen, N. R., Nybo, L., Mellberg, K., Balendran, A., Richter, E. A., & Wojtaszewski, J. F. P. (2019) · Physiological Reports · doi:10.14814/phy2.14307 · Cited by 26 · see citing works
- Authors
- Hunter, R. W., Hughey, C. C., Lantier, L., Sundelin, E. I., Peggie, M., Zeqiraj, E., Sicheri, F., Jessen, N., Wasserman, D. H., & Sakamoto, K.
- Affiliations
- University of Bristol (GB)
- Vanderbilt University (US)
- Aarhus University (DK)
- University of Dundee (GB)
- Mount Sinai Hospital (CA)
- Corresponding author
- Sakamoto, Kei
- ORCID
- Venue
- Nature Medicine
- Published
- 2018-08-27
- Volume
- 24
- Issue
- 9
- Pages
- 1395-1406
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- PMC
- PMC6207338
- OpenAlex
- W2888330909
- Cited by
- 313
- References
- 86
- Citations by year
- 2026: 25 · 2025: 33 · 2024: 47 · 2023: 53 · 2022: 49 · 2021: 33 · 2020: 43 · 2019: 26 · 2018: 4
- FWCI
- 9.51
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- Discovery Research Portal (University of Dundee) (publishedVersion)
- Explore Bristol Research (publishedVersion, other-oa)
- White Rose Research Online (University of Leeds, The University of Sheffield, University of York) (acceptedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Bristol Research (University of Bristol) (submittedVersion, other-oa)
- Funders
- Vanderbilt University (DK059637)
- Wellcome Trust (092381)
- Novo Nordisk
- Danmarks Frie Forskningsfond (4183-00384)
- Novo Nordisk Fonden (NNF13OC0003882, NNF17SA0031230-1)
- Canadian Institutes of Health Research (143277)
- National Institute of Diabetes and Digestive and Kidney Diseases (U2CDK059637, U24DK059637, R37DK050277, P30DK058404)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Rheumatology › Glycogen Storage Diseases and Myoclonus
- Keywords
- metformin, FBP1, hepatic glucose production, gluconeogenesis, AMPK, fructose-2,6-bisphosphate, type 2 diabetes, high-fat diet, euglycemic clamp
- MeSH terms
- Adenosine Monophosphate, Aminoimidazole Carboxamide, Animals, Base Sequence, Chickens, Disease Models, Animal, Glucose, Fructose-Bisphosphatase, Homeostasis, Humans, Hypoglycemia, Liver, Metformin, Mice, Inbred C57BL, Mutation, Obesity, Prodrugs, Ribonucleotides, Glucose Intolerance
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 ›
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