Circulating Fibroblast Growth Factor-21 Is Elevated in Impaired Glucose Tolerance and Type 2 Diabetes and Correlates With Muscle and Hepatic Insulin Resistance
Open accessAbstract
OBJECTIVE: Fibroblast growth factor (FGF)-21 is highly expressed in the liver and regulates hepatic glucose production and lipid metabolism in rodents. However, its role in the pathogenesis of type 2 diabetes in humans remains to be defined. The aim of this study was to quantitate circulating plasma FGF-21 levels and examine their relationship with insulin sensitivity in subjects with varying degrees of obesity and glucose tolerance. RESEARCH DESIGN AND METHODS: Forty-one subjects (8 lean with normal glucose tolerance [NGT], 9 obese with NGT, 12 with impaired fasting glucose [IFG]/impaired glucose tolerance [IGT], and 12 type 2 diabetic subjects) received an oral glucose tolerance test (OGTT) and a hyperinsulinemic-euglycemic clamp (80 mU/m2 per min) combined with 3-[3H] glucose infusion. RESULTS: Subjects with type 2 diabetes, subjects with IGT, and obese subjects with NGT were insulin resistant compared with lean subjects with NGT. Plasma FGF-21 levels progressively increased from 3.9 ± 0.3 ng/ml in lean subjects with NGT to 4.9 ± 0.2 in obese subjects with NGT to 5.2 ± 0.2 in subjects with IGT and to 5.3 ± 0.2 in type 2 diabetic subjects. FGF-21 levels correlated inversely with whole-body (primarily reflects muscle) insulin sensitivity (r = −0.421, P = 0.007) and directly with the hepatic insulin resistance index (r = 0.344, P = 0.034). FGF-21 levels also correlated with measures of glycemia (fasting plasma glucose [r = 0.312, P = 0.05], 2-h plasma glucose [r = 0.414, P = 0.01], and A1C [r = 0.325, P = 0.04]). CONCLUSIONS: Plasma FGF-21 levels are increased in insulin-resistant states and correlate with hepatic and whole-body (muscle) insulin resistance. FGF-21 may play a role in pathogenesis of hepatic and whole-body insulin resistance in type 2 diabetes.
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?
Circulating levels of FGF21 are significantly elevated in humans during type 2 diabetes, obesity, hepatosteatosis, pancreatitis, and mitochondrial dysfunction.
“Circulating levels of FGF21 are significantly elevated in humans during pathophysiological states, including type 2 diabetes (16, 18), obesity (22, 30, 93), hepatosteatosis (30, 79, 146), pancreatitis (117, 137), and mitochondrial dysfunction (78).”
From Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis (2018) · cites this paper as [16]
FGF21 is increased in settings of obesity.
“FGF21 is also increased in settings of obesity”
From FGF21 and the physiological regulation of macronutrient preference (2020) · cites this paper as [134]
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
Prediction of Creatinine Clearance from Serum Creatinine
Cockcroft, D. W., & Gault, H. (2008) · The Nephron journals/Nephron journals · doi:10.1159/000180580 · Cited by 15,291 · see citing works
Glucose clamp technique: a method for quantifying insulin secretion and resistance.
DeFronzo, R. A., Tobin, J. D., & Andres, R. (1979) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1979.237.3.e214 · Cited by 7,425 · see citing works
Self-citationMatsuda, M., & DeFronzo, R. A. (1999) · Diabetes Care · doi:10.2337/diacare.22.9.1462 · Cited by 5,621 · see citing works
Self-citationFGF-21 as a novel metabolic regulator
Kharitonenkov, A., Shiyanova, T. L., Koester, A., Ford, A. M., Micanovic, R., Galbreath, E. J., Sandusky, G. E., Hammond, L. J., Moyers, J. S., Owens, R. A., et al. (2005) · Journal of Clinical Investigation · doi:10.1172/jci23606 · Cited by 2,125 · see citing works
Badman, M. K., Pissios, P., Kennedy, A. R., Koukos, G., Flier, J. S., & Maratos-Flier, E. (2007) · Cell Metabolism · doi:10.1016/j.cmet.2007.05.002 · Cited by 1,495 · see citing works
Xu, J., Lloyd, D. J., Hale, C., Stanislaus, S., Chen, M., Sivits, G., Vonderfecht, S., Hecht, R., Li, Y.-S., Lindberg, R. A., et al. (2009) · Diabetes · doi:10.2337/db08-0392 · Cited by 1,151 · see citing works
Advances in Male Contraception
Page, S. T., Amory, J. K., & Bremner, W. J. (2008) · Endocrine Reviews · doi:10.1210/er.2007-0041 · Cited by 1,134 · see citing works
Zhang, X., Yeung, D. C. Y., Karpisek, M., Stejskal, D., Zhou, Z.-G., Liu, F., Wong, R. L. C., Chow, W.-S., Tso, A. W. K., Lam, K. S. L., et al. (2008) · Diabetes · doi:10.2337/db07-1476 · Cited by 908 · see citing works
Identification of a novel FGF, FGF-21, preferentially expressed in the liver
Nishimura, T., Nakatake, Y., Konishi, M., & Itoh, N. (2000) · Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression · doi:10.1016/s0167-4781(00)00067-1 · Cited by 847 · see citing works
Measurement of Size and Turnover Rate of Body Glucose Pool by the Isotope Dilution Method
Steele, R., Wall, J. S., de Bodo, R. C., & Altszuler, N. (1956) · American Journal of Physiology-Legacy Content · doi:10.1152/ajplegacy.1956.187.1.15 · Cited by 816 · see citing works
Groop, L. C., Bonadonna, R. C., DelPrato, S., Ratheiser, K., Zyck, K., Ferrannini, E., & DeFronzo, R. A. (1989) · Journal of Clinical Investigation · doi:10.1172/jci114142 · Cited by 812 · see citing works
Self-citationKurosu, H., Choi, M., Ogawa, Y., Dickson, A. S., Goetz, R., Eliseenkova, A. V., Mohammadi, M., Rosenblatt, K. P., Kliewer, S. A., & Kuro-o, M. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m704165200 · Cited by 748 · see citing works
The metabolic state of diabetic monkeys is regulated by fibroblast growth factor-21
Kharitonenkov, A., Wroblewski, V. J., Koester, A., Chen, Y.-F., Clutinger, C. K., Tigno, X. T., Hansen, B. C., Shanafelt, A. B., & Etgen, G. J. (2007) · Endocrinology · doi:10.1210/en.2006-1168 · Cited by 738 · see citing works
Fu, L., John, L. M., Adams, S. H., Yu, X. X., Tomlinson, E., Renz, M. E., Williams, P. M., Soriano, R. H., Corpuz, R. T., Moffat, B., et al. (2004) · Endocrinology · doi:10.1210/en.2003-1671 · Cited by 580 · see citing works
Tomlinson, E., Fu, L., John, L., Hultgren, B., Huang, X., Renz, M., Stephan, J. P., Tsai, S. P., Powell-Braxton, L., French, D., et al. (2002) · Endocrinology · doi:10.1210/endo.143.5.8850 · Cited by 576 · see citing works
Goetz, R., Beenken, A., Ibrahimi, O., Kalinina, J., Olsen, S., Eliseenkova, A. V., Xu, C.-F., Neubert, T., Zhang, F.-M., Linhardt, R., et al. (2007) · Molecular and Cellular Biology · doi:10.1128/mcb.02249-06 · Cited by 544 · see citing works
Fibroblast Growth Factor Signaling during Early Vertebrate Development
Böttcher, R. T., & Niehrs, C. (2005) · Endocrine Reviews · doi:10.1210/er.2003-0040 · Cited by 540 · see citing works
FGF23, PHEX, and MEPE regulation of phosphate homeostasis and skeletal mineralization
Quarles, L. D. (2003) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00016.2003 · Cited by 335 · see citing works
FGF‐21/FGF‐21 receptor interaction and activation is determined by βKlotho
Kharitonenkov, A., Dunbar, J. D., Bina, H. A., Bright, S. W., Moyers, J. S., Zhang, C., Ding, L., Micanovic, R., Mehrbod, S. F., Knierman, M. D., et al. (2007) · Journal of Cellular Physiology · doi:10.1002/jcp.21357 · Cited by 329 · see citing works
FGF21 attenuates lipolysis in human adipocytes – A possible link to improved insulin sensitivity
Arner, P., Pettersson, A., Mitchell, P. J., Dunbar, J. D., Kharitonenkov, A., & Rydén, M. (2008) · FEBS Letters · doi:10.1016/j.febslet.2008.04.038 · Cited by 234 · see citing works
Molecular determinants of FGF‐21 activity—synergy and cross‐talk with PPARγ signaling
Moyers, J. S., Shiyanova, T. L., Mehrbod, F., Dunbar, J. D., Noblitt, T. W., Otto, K. A., Reifel-Miller, A. E., & Kharitonenkov, A. (2006) · Journal of Cellular Physiology · doi:10.1002/jcp.20847 · Cited by 193 · see citing works
Chen, W.-W., Li, L., Yang, G.-Y., Li, K., Qi, X.-Y., Zhu, W., Tang, Y., Liu, H., & Boden, G. (2007) · Experimental and Clinical Endocrinology & Diabetes · doi:10.1055/s-2007-985148 · Cited by 186 · see citing works
Role of free fatty acids and insulin in determining free fatty acid and lipid oxidation in man.
Groop, P., Bonadonna, R. C., shank, M. L., Petrides, A. S., & DeFronzo, R. A. (1991) · Journal of Clinical Investigation · doi:10.1172/jci115005 · Cited by 180 · see citing works
Self-citationRegulation of hepatic glucose metabolism in humans
DeFronzo, R. A., & Ferrannini, E. (1987) · Diabetes/Metabolism Reviews · doi:10.1002/dmr.5610030204 · Cited by 167 · see citing works
Self-citationPlasma Concentrations of Fibroblast Growth Factors 19 and 21 in Patients with Anorexia Nervosa
Dostálová, I., Kaválková, P., Haluzíková, D., Lacinová, Z., Mráz, M., Papežová, H., & Haluzı́k, M. (2008) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2008-0746 · Cited by 111 · see citing works
Serum Levels of the Adipokine FGF21 Depend on Renal Function
Stein, S., Bachmann, A., Lössner, U., Kratzsch, J., Blüher, M., Stümvoll, M., & Faßhauer, M. (2008) · Diabetes Care · doi:10.2337/dc08-1054 · Cited by 111 · see citing works
Huang, X., Yu, C., Jin, C., Yang, C., Xie, R., Cao, D., Wang, F., & McKeehan, W. L. (2006) · Molecular Carcinogenesis · doi:10.1002/mc.20241 · Cited by 110 · see citing works
Fibroblast Growth Factor-21 as a Therapeutic Agent for Metabolic Diseases
Kharitonenkov, A., & Shanafelt, A. B. (2008) · BioDrugs · doi:10.2165/00063030-200822010-00004 · Cited by 98 · see citing works
Plasma FGF-21 levels in type 2 diabetic patients with ketosis
Li, L., Yang, G., Ning, H., Yang, M., Liu, H., & Chen, W. (2008) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2008.07.012 · Cited by 55 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Mechanisms of Insulin Action and Insulin Resistance
Petersen, M. C., & Shulman, G. I. (2018) · Physiological Reviews · doi:10.1152/physrev.00063.2017 · Cited by 3,028 · see citing works
Koliaki, C., Szendroedi, J., Kaul, K., Jelenik, T., Nowotny, P., Jankowiak, F., Herder, C., Carstensen, M., Krausch, M., Knoefel, W. T., et al. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.04.004 · Cited by 1,032 · see citing works
Understanding the Physiology of FGF21
Fisher, F. M., & Maratos-Flier, E. (2016) · Annual Review of Physiology · doi:10.1146/annurev-physiol-021115-105339 · Cited by 912 · see citing works
The effects of LY2405319, an FGF21 analog, in obese human subjects with type 2 diabetes
Gaich, G., Chien, J. Y., Fu, H., Glass, L. C., Deeg, M. A., Holland, W. L., Kharitonenkov, A., Bumol, T., Schilske, H. K., & Moller, D. E. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.08.005 · Cited by 885 · see citing works
Basic Mechanisms of Diabetic Heart Disease
Ritchie, R. H., & Abel, E. D. (2020) · Circulation Research · doi:10.1161/circresaha.120.315913 · Cited by 730 · see citing works
Metabolites as regulators of insulin sensitivity and metabolism
Yang, Q., Vijayakumar, A., & Kahn, B. B. (2018) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-018-0044-8 · Cited by 681 · see citing works
Hepatokines: Linking nonalcoholic fatty liver disease and insulin resistance
Meex, R. C. R., & Watt, M. J. (2017) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2017.56 · Cited by 631 · see citing works
Increased Fibroblast Growth Factor 21 in Obesity and Nonalcoholic Fatty Liver Disease
Dushay, J., Chui, P. C., Gopalakrishnan, G. S., Varela–Rey, M., Crawley, M., Fisher, F. M., Badman, M. K., Martinez–Chantar, M. L., & Maratos–Flier, E. (2010) · Gastroenterology · doi:10.1053/j.gastro.2010.04.054 · Cited by 607 · see citing works
FGF21 is an endocrine signal of protein restriction
Laeger, T., Henagan, T. M., Albarado, D. C., Redman, L. M., Bray, G. A., Noland, R. C., Münzberg, H., Hutson, S. M., Gettys, T. W., Schwartz, M. W., et al. (2014) · Journal of Clinical Investigation · doi:10.1172/jci74915 · Cited by 593 · see citing works
Adipokine dysregulation and adipose tissue inflammation in human obesity
Unamuno, X., Gómez‐Ambrosi, J., Rodríguez, A., Becerril, S., Frühbeck, G., & Catalán, V. (2018) · European Journal of Clinical Investigation · doi:10.1111/eci.12997 · Cited by 610 · see citing works
Emerging therapeutic approaches for the treatment of NAFLD and type 2 diabetes mellitus
Ferguson, D., & Finck, B. N. (2021) · Nature Reviews Endocrinology · doi:10.1038/s41574-021-00507-z · Cited by 507 · see citing works
Fructose metabolism and metabolic disease
Hannou, S. A., Haslam, D. E., McKeown, N. M., & Herman, M. A. (2018) · Journal of Clinical Investigation · doi:10.1172/jci96702 · Cited by 561 · see citing works
Endocrine fibroblast growth factors 15/19 and 21: from feast to famine
Potthoff, M. J., Kliewer, S. A., & Mangelsdorf, D. J. (2012) · Genes & Development · doi:10.1101/gad.184788.111 · Cited by 442 · see citing works
Li, H., Fang, Q., Gao, F., Fan, J., Zhou, J., Wang, X., Zhang, H., Pan, X., Bao, Y., Xiang, K., et al. (2010) · Journal of Hepatology · doi:10.1016/j.jhep.2010.05.018 · Cited by 400 · see citing works
Hondares, E., Rosell, M., Gonzalez, F. J., Giralt, M., Iglesias, R., & Villarroya, F. (2010) · Cell Metabolism · doi:10.1016/j.cmet.2010.02.001 · Cited by 377 · see citing works
Metabolic syndrome and nonalcoholic fatty liver disease: Is insulin resistance the link?
Asrih, M., & Jornayvaz, F. R. (2015) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2015.02.018 · Cited by 331 · see citing works
FGF21 as Modulator of Metabolism in Health and Disease
Tezze, C., Romanello, V., & Sandri, M. (2019) · Frontiers in Physiology · doi:10.3389/fphys.2019.00419 · Cited by 313 · see citing works
Fibroblast Growth Factor 21 as an emerging metabolic regulator: clinical perspectives
Woo, Y. C., Xu, A., Wang, Y., & Lam, K. S. L. (2012) · Clinical Endocrinology · doi:10.1111/cen.12095 · Cited by 302 · see citing works
Adipo-myokines: two sides of the same coin–mediators of inflammation and mediators of exercise
Raschke, S., & Eckel, J. (2013) · Mediators of Inflammation · doi:10.1155/2013/320724 · Cited by 296 · see citing works
Fibroblast Growth Factor 21—Metabolic Role in Mice and Men
Staiger, H., Keuper, M., Berti, L., Hrabě de Angelis, M., & Häring, H.-U. (2017) · Endocrine Reviews · doi:10.1210/er.2017-00016 · Cited by 270 · see citing works
Hepatokines and metabolism: Deciphering communication from the liver
Jensen-Cody, S. O., & Potthoff, M. J. (2021) · Molecular Metabolism · doi:10.1016/j.molmet.2020.101138 · Cited by 252 · see citing works
Fructose ingestion acutely stimulates circulating FGF21 levels in humans
Dushay, J. R., Toschi, E., Mitten, E. K., Fisher, F. M., Herman, M. A., & Maratos-Flier, E. (2015) · Molecular Metabolism · doi:10.1016/j.molmet.2014.09.008 · Cited by 233 · see citing works
Besse-Patin, A., Montastier, E., Vinel, C., Castan-Laurell, I., Louche, K., Dray, C., Daviaud, D., Mir, L., Marques, M.-A., Thalamas, C., et al. (2014) · International Journal of Obesity · doi:10.1038/ijo.2013.158 · Cited by 227 · see citing works
Cellular Mechanisms by Which FGF21 Improves Insulin Sensitivity in Male Mice
Camporez, J. P., Jornayvaz, F. R., Petersen, M. C., Pesta, D. H., Guigni, B. A., Serr, J., Zhang, D., Kahn, M., Samuel, V. T., Jurczak, M. J., et al. (2013) · Endocrinology · doi:10.1210/en.2013-1191 · Cited by 226 · see citing works
Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis
BonDurant, L. D., & Potthoff, M. J. (2018) · Annual Review of Nutrition · doi:10.1146/annurev-nutr-071816-064800 · Cited by 222 · see citing works
Jornayvaz, F. R., Jurczak, M. J., Lee, H., Birkenfeld, A. L., Frederick, D. W., Zhang, D., Zhang, X., Samuel, V. T., & Shulman, G. I. (2010) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00361.2010 · Cited by 212 · see citing works
Gallego-Escuredo, J. M., Gómez‐Ambrosi, J., Catalán, V., Domingo, P., Giralt, M., Frühbeck, G., & Villarroya, F. (2014) · International Journal of Obesity · doi:10.1038/ijo.2014.76 · Cited by 212 · see citing works
Circulating fibroblast growth factors as metabolic regulators--a critical appraisal.
Angelin, B., Larsson, T., & Rudling, M. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.11.001 · Cited by 210 · see citing works
Wölnerhanssen, B. K., Peterli, R., Steinert, R. E., Peters, T. T. A., Borbély, Y., & Beglinger, C. (2011) · Surgery for Obesity and Related Diseases · doi:10.1016/j.soard.2011.01.044 · Cited by 206 · see citing works
Biomarkers of insulin sensitivity and insulin resistance: Past, present and future
Park, S. E., Park, C., & Sweeney, G. (2015) · Critical Reviews in Clinical Laboratory Sciences · doi:10.3109/10408363.2015.1023429 · Cited by 209 · see citing works
Chow, W. S., Xu, A., Woo, Y. C., Tso, A. W. K., Cheung, S., Fong, C. H.-Y., Tse, H., Chau, M. T., Cheung, B. M. Y., & Lam, K. S. L. (2013) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.113.301599 · Cited by 193 · see citing works
Li, H., Gao, Z., Zhang, J., Ye, X., Xu, A., Ye, J., & Jia, W. (2012) · Diabetes · doi:10.2337/db11-0846 · Cited by 193 · see citing works
Crosstalk between adipokines and myokines in fat browning
Rodrı́guez, A., Becerril, S., Ezquerro, S., Méndez-Giménez, L., & Frühbeck, G. (2016) · Acta Physiologica · doi:10.1111/apha.12686 · Cited by 192 · see citing works
Jiang, S., Cheng, Y., Fang, Q., Shao, M., Zhang, Y., Liu, Y., Deng, Y., Shan, B., Liu, J., Li, H., et al. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.565960 · Cited by 183 · see citing works
High Plasma Level of Fibroblast Growth Factor 21 Is an Independent Predictor of Type 2 Diabetes
Chen, C., Cheung, B. M. Y., Tso, A. W. K., Wang, Y., Law, L. S., Ong, K. L., Wat, N. M. S., Xu, A., & Lam, K. S. L. (2011) · Diabetes Care · doi:10.2337/dc11-0294 · Cited by 181 · see citing works
Exercise increases serum fibroblast growth factor 21 (FGF21) levels
Cuevas-Ramos, D., Almeda-Valdés, P., Meza-Arana, C. E., Brito-Córdova, G., Gómez-Pérez, F. J., Mehta, R., Oseguera-Moguel, J., & Aguilar-Salinas, C. A. (2012) · PLoS ONE · doi:10.1371/journal.pone.0038022 · Cited by 178 · see citing works
Yu, H., Xia, F., Lam, K. S., Wang, Y., Bao, Y., Zhang, J., Gu, Y., Zhou, P., Lu, J., Jia, W., et al. (2011) · Clinical Chemistry · doi:10.1373/clinchem.2010.155184 · Cited by 170 · see citing works
Gómez‐Ambrosi, J., Gallego-Escuredo, J. M., Catalán, V., Rodrı́guez, A., Domingo, P., Moncada, R., Valentí, V., Salvador, J., Giralt, M., Villarroya, F., et al. (2016) · Clinical Nutrition · doi:10.1016/j.clnu.2016.04.027 · Cited by 168 · see citing works
Going Back to the Biology of FGF21: New Insights
Lewis, J. E., Ebling, F. J. P., Samms, R. J., & Tsintzas, K. (2019) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2019.05.007 · Cited by 164 · see citing works
van Deuren, T., Blaak, E. E., & Canfora, E. E. (2022) · Obesity Reviews · doi:10.1111/obr.13498 · Cited by 162 · see citing works
Fibroblast growth factor-21, energy balance and obesity
Giralt, M., Gavaldà‐Navarro, A., & Villarroya, F. (2015) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2015.09.018 · Cited by 146 · see citing works
Yang, S. J., Hong, H. C., Choi, H. Y., Yoo, H. J., Cho, G. J., Hwang, T. G., Baik, S. H., Choi, D. S., Kim, S. M., & Choi, K. M. (2011) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2011.04078.x · Cited by 148 · see citing works
Pan, Q., Lin, S., Li, Y., Liu, L., Li, X., Gao, X., Yan, J., Gu, B., Chen, X., Li, W., et al. (2020) · EBioMedicine · doi:10.1016/j.ebiom.2020.103202 · Cited by 138 · see citing works
Liu, J., Xu, Y., Hu, Y., & Wang, G. (2014) · Metabolism · doi:10.1016/j.metabol.2014.11.009 · Cited by 137 · see citing works
Kim, H., Méndez, R., Zheng, Z., Chang, L., Cai, J., Zhang, R., & Zhang, K. (2014) · Endocrinology · doi:10.1210/en.2013-1490 · Cited by 134 · see citing works
PGC-1α negatively regulates hepatic FGF21 expression by modulating the heme/Rev-Erbα axis
Estall, J. L., Ruas, J. L., Choi, C. S., Laznik, D., Badman, M. K., Maratos–Flier, E., Shulman, G. I., & Spiegelman, B. M. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0912533106 · Cited by 133 · see citing works
Feingold, K. R., Grünfeld, C., Heuer, J. G., Gupta, A., Cramer, M. S., Zhang, T., Shigenaga, J. K., Patzek, S. M., Chan, Z. W., Moser, A. H., et al. (2012) · Endocrinology · doi:10.1210/en.2011-1496 · Cited by 130 · see citing works
Dnmt3a is an epigenetic mediator of adipose insulin resistance
You, D., Nilsson, E., Tenen, D. E., Lyubetskaya, A., Lo, J. C., Jiang, R., Deng, J., Dawes, B. A., Vaag, A. A., Ling, C., et al. (2017) · eLife · doi:10.7554/elife.30766 · Cited by 124 · see citing works
The role of adipokines in skeletal muscle inflammation and insulin sensitivity
Nicholson, T. A., Church, C., Baker, D. J., & Jones, S. W. (2018) · Journal of Inflammation · doi:10.1186/s12950-018-0185-8 · Cited by 128 · see citing works
Fibroblast Growth Factor 21 Predicts the Metabolic Syndrome and Type 2 Diabetes in Caucasians
Bobbert, T., Schwarz, F., Fischer‐Rosinsky, A., Pfeiffer, A. F. H., Möhlig, M., Mai, K., & Spranger, J. (2012) · Diabetes Care · doi:10.2337/dc12-0703 · Cited by 125 · see citing works
Glucagon-to-insulin ratio is pivotal for splanchnic regulation of FGF-21 in humans
Hansen, J. S., Clemmesen, J. O., Secher, N. H., Hoene, M., Drescher, A., Weigert, C., Pedersen, B. K., & Plomgaard, P. (2015) · Molecular Metabolism · doi:10.1016/j.molmet.2015.06.001 · Cited by 123 · see citing works
Role of autophagy in the pathophysiology of nonalcoholic fatty liver disease: A controversial issue
Kwanten, W. J. (2014) · World Journal of Gastroenterology · doi:10.3748/wjg.v20.i23.7325 · Cited by 113 · see citing works
Iglesias, P., Selgas, R., Romero, S., & Díez, J. J. (2012) · European Journal of Endocrinology · doi:10.1530/eje-12-0357 · Cited by 113 · see citing works
Zhang, Y., Lei, T., Huang, J., Wang, S. B., Zhou, L., Yang, Z., & Chen, X. (2011) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2011.05.003 · Cited by 110 · see citing works
Samson, S. L., Sathyanarayana, P., Jogi, M., Gonzalez, E. V., Gutierrez, A., Krishnamurthy, R., Muthupillai, R., Chan, L., & Bajaj, M. (2011) · Diabetologia · doi:10.1007/s00125-011-2317-z · Cited by 110 · see citing works
So, W. Y., Cheng, Q., Chen, L., Evans‐Molina, C., Xu, A., Lam, K. S. L., & Leung, P. S. (2013) · Diabetes · doi:10.2337/db13-0645 · Cited by 109 · see citing works
Hansen, J. S., Pedersen, B. K., Xu, G., Lehmann, R., Weigert, C., & Plomgaard, P. (2016) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2016-1681 · Cited by 106 · see citing works
Regulation of FGF21 Expression and Secretion by Retinoic Acid Receptor-related Orphan Receptor α
Wang, Y., Solt, L. A., & Burris, T. P. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.102160 · Cited by 106 · see citing works
ATF4- and CHOP-Dependent Induction of FGF21 through Endoplasmic Reticulum Stress
Wan, X., Lu, X., Xiao, Y.-C., Lin, Y., Zhu, H., Ding, T., Yang, Y., Huang, Y., Zhang, Y., Liu, Y., et al. (2014) · BioMed Research International · doi:10.1155/2014/807874 · Cited by 105 · see citing works
Tong, X., Muchnik, M., Chen, Z., Patel, M., Wu, N., Joshi, S., Rui, L., Lazar, M. A., & Yin, L. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.172866 · Cited by 105 · see citing works
Distinct Changes in Serum Fibroblast Growth Factor 21 Levels in Different Subtypes of Diabetes
Xiao, Y., Xu, A., Law, L. S., Chen, C., Li, H., Li, X., Yang, L., Liu, S., Zhou, Z., & Lam, K. S. L. (2011) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2011-1930 · Cited by 102 · see citing works
Qin, Y., Zhou, Y. G., Chen, S., Zhao, X.-L., Ran, L., Zeng, X.-L., Wu, Y., Chen, J., Kang, C., Shu, F., et al. (2015) · PLoS ONE · doi:10.1371/journal.pone.0133496 · Cited by 101 · see citing works
Dong, J. Q., Rossulek, M. I., Somayaji, V. R., Baltrukonis, D. J., Liang, Y., Hudson, K. J., Hernandez‐Illas, M., & Calle, R. A. (2015) · British Journal of Clinical Pharmacology · doi:10.1111/bcp.12676 · Cited by 100 · see citing works
FGF21 and the physiological regulation of macronutrient preference
Hill, C. M., Qualls-Creekmore, E., Berthoud, H.-R., Soto, P., Yu, S., McDougal, D. H., Münzberg, H., & Morrison, C. D. (2020) · Endocrinology · doi:10.1210/endocr/bqaa019 · Cited by 99 · see citing works
Uebanso, T., Taketani, Y., Yamamoto, H., Amo, K., Ominami, H., Arai, H., Takei, Y., Masuda, M., Tanimura, A., Harada, N., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0022976 · Cited by 99 · see citing works
Morrow, R. M., Picard, M. A., Derbeneva, O. A., Leipzig, J. N., McManus, M. J., Gouspillou, G., Barbat‐Artigas, S., Santos, C. D., Hepple, R. T., Murdock, D. G., et al. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1700997114 · Cited by 96 · see citing works
Henriksson, E., & Andersen, B. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.601349 · Cited by 95 · see citing works
Fibroblast growth factor 21 is a metabolic regulator that plays a role in the adaptation to ketosis
Domouzoglou, E. M., & Maratos–Flier, E. (2011) · American Journal of Clinical Nutrition · doi:10.3945/ajcn.110.001941 · Cited by 93 · see citing works
Of rodents and men: Species-specific glucose regulation and type 2 diabetes research
Chandrasekera, P. C. (2014) · ALTEX · doi:10.14573/1309231 · Cited by 89 · see citing works
Fibroblast Growth Factor 21 and the Adaptive Response to Nutritional Challenges
Martínez‐Garza, Ú., Torres‐Oteros, D., Yarritu, A., Marrero, P. F., Haro, D., & Relat, J. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20194692 · Cited by 87 · see citing works
Fibroblast Growth Factor 21 As an Emerging Therapeutic Target for Type 2 Diabetes Mellitus
So, W. Y., & Leung, P. S. (2016) · Medicinal Research Reviews · doi:10.1002/med.21390 · Cited by 85 · see citing works
Murata, Y., Konishi, M., & Itoh, N. (2011) · Journal of Nutrition and Metabolism · doi:10.1155/2011/981315 · Cited by 85 · see citing works
Lee, C., Hui, E. Y. L., Woo, Y. C., Yeung, C., Chow, W. S., Yuen, M. M. A., Fong, C. H.-Y., Xu, A., & Lam, K. S. L. (2015) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2014-3465 · Cited by 84 · see citing works
Ong, K. L., Rye, K., O'Connell, R. L., Jenkins, A. J., Brown, C. S. B., Xu, A., SULLIVAN, D. R., Barter, P. J., KEECH, A. C., & on behalf of the FIELD study investigators (2012) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2012-2267 · Cited by 82 · see citing works
Conte, M., Sabbatinelli, J., Chiariello, A., Martucci, M., Santoro, A., Monti, D., Arcaro, M., Galimberti, D., Scarpini, E. A., Bonfigli, A. R., et al. (2020) · GeroScience · doi:10.1007/s11357-020-00287-w · Cited by 82 · see citing works
Obesity as the common soil of non‐alcoholic fatty liver disease and diabetes: Role of adipokines
Hui, E., Xu, A., Yang, H. B., & Lam, K. S. L. (2013) · Journal of Diabetes Investigation · doi:10.1111/jdi.12093 · Cited by 79 · see citing works
Serum levels of fibroblast growth factor‐21 are increased in chronic and acute renal dysfunction
Hindricks, J., Ebert, T., Bachmann, A., Kralisch, S., Lössner, U., Kratzsch, J., Stolzenburg, J., Dietel, A., Beige, J., Anders, M. S., et al. (2013) · Clinical Endocrinology · doi:10.1111/cen.12380 · Cited by 79 · see citing works
Song, H., Chu, Q., Xu, D., Xu, Y., & Zheng, X. (2015) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.5b05177 · Cited by 77 · see citing works
Asrih, M., Altirriba, J., Rohner‐Jeanrenaud, F., & Jornayvaz, F. R. (2015) · PLoS ONE · doi:10.1371/journal.pone.0126364 · Cited by 75 · see citing works
Xiao, Y., Liu, L., Xu, A., Zhou, P., Long, Z., Tu, Y., Chen, X., Tang, W., Huang, G., & Zhou, Z. (2015) · Cardiovascular Diabetology · doi:10.1186/s12933-015-0229-9 · Cited by 75 · see citing works
Stressed Liver and Muscle Call on Adipocytes with FGF21
Luo, Y., & McKeehan, W. L. (2013) · Frontiers in Endocrinology · doi:10.3389/fendo.2013.00194 · Cited by 75 · see citing works
Feraco, A., Gorini, S., Armani, A., Camajani, E., Rizzo, M., & Caprio, M. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22179327 · Cited by 74 · see citing works
Plasma FGF21 displays a circadian rhythm during a 72‐h fast in healthy female volunteers
Andersen, B., Beck‐Nielsen, H., & Højlund, K. (2011) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2011.04084.x · Cited by 74 · see citing works
Berti, L., Irmler, M., Zdichavsky, M., Meile, T., Böhm, A., Stefan, N., Fritsche, A., Beckers, J., Königsrainer, A., Häring, H.-U., et al. (2015) · Molecular Metabolism · doi:10.1016/j.molmet.2015.04.002 · Cited by 73 · see citing works
Implication of hepatokines in metabolic disorders and cardiovascular diseases
Jung, T. W., Yoo, H. J., & Choi, K. M. (2016) · BBA Clinical · doi:10.1016/j.bbacli.2016.03.002 · Cited by 71 · see citing works
Song, H., Zheng, Z., Wu, J., Lai, J., Chu, Q., & Zheng, X. (2016) · PLoS ONE · doi:10.1371/journal.pone.0149670 · Cited by 73 · see citing works
Semba, R. D., Sun, K., Egan, J. M., Crasto, C., Carlson, O. D., & Ferrucci, L. (2012) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2011-2823 · Cited by 70 · see citing works
Fibroblast Growth Factor 21 Analogs for Treating Metabolic Disorders
Zhang, J., & Li, Y. (2015) · Frontiers in Endocrinology · doi:10.3389/fendo.2015.00168 · Cited by 70 · see citing works
Functional compounds in dragon fruit peels and their potential health benefits: a review
Le, N. L. (2021) · International Journal of Food Science & Technology · doi:10.1111/ijfs.15111 · Cited by 69 · see citing works
Fibroblast growth factor 21: a novel metabolic regulator from pharmacology to physiology
Li, H., Zhang, J., & Jia, W. (2013) · Frontiers of Medicine · doi:10.1007/s11684-013-0244-8 · Cited by 69 · see citing works
Kruse, R., Vienberg, S. G., Vind, B. F., Andersen, B., & Højlund, K. (2017) · Diabetologia · doi:10.1007/s00125-017-4373-5 · Cited by 69 · see citing works
Bifari, F., Manfrini, R., Dei, M., Berra, C., Siano, M., Zuin, M. G., Paroni, R. C., & Folli, F. B. (2018) · Pharmacological Research · doi:10.1016/j.phrs.2018.09.025 · Cited by 69 · see citing works
Self-citationHomeostatic sensing of dietary protein restriction: a case for FGF21
Hill, C. M., Berthoud, H.-R., Münzberg, H., & Morrison, C. D. (2018) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2018.06.002 · Cited by 68 · see citing works
FGF21 resistance is not mediated by downregulation of beta-klotho expression in white adipose tissue
Markan, K. R., Naber, M. C., Small, S. M., Peltekian, L., Kessler, R. L., & Potthoff, M. J. (2017) · Molecular Metabolism · doi:10.1016/j.molmet.2017.03.009 · Cited by 68 · see citing works
Yang, M., Zhang, L., Wang, C., Liu, H., Boden, G. H., Yang, G., & Li, L. (2012) · PLoS ONE · doi:10.1371/journal.pone.0048392 · Cited by 67 · see citing works
Association between circulating fibroblast growth factor 21 and mortality in end-stage renal disease
Kohara, M., Masuda, T., Shiizaki, K., Akimoto, T., Watanabe, Y., Honma, S., Sekiguchi, C., Miyazawa, Y., Kusano, E., Kanda, Y., et al. (2017) · PLoS ONE · doi:10.1371/journal.pone.0178971 · Cited by 66 · see citing works
FGF21 Is an Insulin-Dependent Postprandial Hormone in Adult Humans
Samms, R. J., Lewis, J. E., Norton, L., Stephens, F. B., Gaffney, C. J., Butterfield, T., Smith, D. P., Cheng, C. C., Perfield, J. W., Adams, A. C., et al. (2017) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2017-01257 · Cited by 65 · see citing works
Lips, M. A., de Groot, G. H., Berends, F. J., Wiezer, M. J., van Wagensveld, B. A., Swank, D. J., Luijten, A. A. P. M., van Dijk, K. W., Pijl, H., Jansen, P. L. M., et al. (2014) · Clinical Endocrinology · doi:10.1111/cen.12496 · Cited by 65 · see citing works
Increased FGF21 plasma levels in humans with sepsis and SIRS
Gariani, K., Drifte, G., Dunn-Siegrist, I., Pugin, J., & Jornayvaz, F. R. (2013) · Endocrine Connections · doi:10.1530/ec-13-0040 · Cited by 65 · see citing works
FGF21 as a mediator of adaptive responses to stress and metabolic benefits of anti-diabetic drugs
Kim, K. H., & Lee, M. (2015) · Journal of Endocrinology · doi:10.1530/joe-15-0160 · Cited by 63 · see citing works
- Authors
- Chavez, A. O., Molina-Carrion, M., Abdul-Ghani, M. A., Folli, F., DeFronzo, R. A., & Tripathy, D.
- Affiliations
- From the Division of Diabetes, The University of Texas Health Science Center at San Antonio, San Antonio, Texas.
- The University of Texas at San Antonio Health Science Center (US)
- Corresponding author
- Tripathy, Devjit
- Venue
- Diabetes Care
- Publisher
- American Diabetes Association
- Published
- 2009-06-01
- Volume
- 32
- Issue
- 8
- Pages
- 1542-1546
- ISSN
- 0149-5992 (ISSN-L)
- 1935-5548
- PMC
- PMC2713625
- OpenAlex
- W2131044927
- Cited by
- 390
- References
- 29
- Citations by year
- 2026: 5 · 2025: 12 · 2024: 24 · 2023: 32 · 2022: 22 · 2021: 30 · 2020: 30 · 2019: 24 · 2018: 30 · 2017: 27 · 2016: 32 · 2015: 33 · 2014: 17 · 2013: 22 · 2012: 18
- FWCI
- 6.72
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Diabetes Care (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fibroblast Growth Factor Research
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- FGF21, type 2 diabetes, impaired glucose tolerance, insulin resistance, hepatic insulin resistance, skeletal muscle insulin sensitivity, obesity, impaired fasting glucose, glycemia, hyperinsulinemic-euglycemic clamp
- MeSH terms
- Adult, Blood Pressure, Diabetes Mellitus, Type 2, Fibroblast Growth Factors, Glucose Tolerance Test, Humans, Insulin Resistance, Liver, Middle Aged, Obesity, Reference Values, Glucose Clamp Technique, Body Mass Index, Glucose Intolerance, Muscle, Skeletal
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
