Circulating follistatin is liver-derived and regulated by the glucagon-to-insulin ratio
Open accessAbstract
CONTEXT: Follistatin is a plasma protein recently reported to increase under conditions with negative energy balance, such as exercise and fasting in humans. Currently, the perception is that circulating follistatin is a result of para/autocrine actions from various tissues. The large and acute increase in circulating follistatin in response to exercise suggests that it may function as an endocrine signal. OBJECTIVE: We assessed origin and regulation of circulating follistatin in humans. DESIGN/INTERVENTIONS: First, we assessed arterial-to-venous difference of follistatin over the splanchnic bed at rest and during exercise in healthy humans. To evaluate the regulation of plasma follistatin we manipulated glucagon-to-insulin ratio in humans at rest as well as in cultured hepatocytes. Finally, the impact of follistatin on human islets of Langerhans was assessed. RESULTS: We demonstrate that in humans the liver is a major contributor to circulating follistatin both at rest and during exercise. Glucagon increases and insulin inhibits follistatin secretion both in vivo and in vitro, mediated via the secondary messenger cAMP in the hepatocyte. Short-term follistatin treatment reduced glucagon secretion from islets of Langerhans, whereas long-term follistatin treatment prevented apoptosis and induced proliferation of rat β cells. CONCLUSIONS: In conclusion, in humans, the liver secretes follistatin at rest and during exercise, and the glucagon-to-insulin ratio is a key determinant of circulating follistatin levels. Circulating follistatin may be a marker of the glucagon-to-insulin tone on the liver.
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?
Follistatin is an exercise-inducible hepatokine that increases transitorily in the recovery period after a bout of exercise.
“Studies in humans have identified follistatin as an exercise-inducible hepatokine that increases transitorily in the recovery period after a bout of exercise [117,134,183].”
Other exercise-induced factors, such as irisin, follistatin, and OCN, directly protect β-cells from damage, further potentiating their beneficial metabolic properties.
“Concurrently, other exercise-induced factors, such as irisin [66], follistatin [183], and OCN [209], directly protect β-cells from damage, further potentiating their beneficial metabolic properties.”
Under conditions of prolonged fasting or increased energy demands, FST is significantly upregulated in response to increased and decreased amounts of glucagon and insulin, respectively.
“Under conditions of prolonged fasting or increased energy demands (such as exercise), FST is significantly upregulated in response to increased and decreased amounts of glucagon and insulin, respectively [190].”
From Hepatokines and metabolism: Deciphering communication from the liver (2021) · cites this paper as [190]
FST is thought to be acutely regulated by the glucagon-to-insulin ratio.
“it is thought that FST is acutely regulated by the glucagon-to-insulin ratio [190].”
From Hepatokines and metabolism: Deciphering communication from the liver (2021) · cites this paper as [190]
The liver is a key contributor to circulating levels of FST in humans.
“recent work indicated that the liver is a key contributor to circulating levels of FST in humans [[188], [189], [190]].”
From Hepatokines and metabolism: Deciphering communication from the liver (2021) · cites this paper as [190]
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
Regulation of myostatin activity and muscle growth
Lee, S.-J., & McPherron, A. C. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.151270098 · Cited by 1,616 · see citing works
Activin-Binding Protein from Rat Ovary Is Follistatin
Nakamura, T., Takio, K., Eto, Y., Shibai, H., Titani, K., & Sugino, H. (1990) · Science · doi:10.1126/science.2106159 · Cited by 883 · see citing works
GLUT2, glucose sensing and glucose homeostasis
Thorens, B. (2015) · Diabetologia · doi:10.1007/s00125-014-3451-1 · Cited by 722 · see citing works
The role of hepatokines in metabolism
Stefan, N., & Häring, H.-U. (2013) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2012.258 · Cited by 500 · see citing works
Iemura, S.-I., Yamamoto, T. S., Takagi, C., Uchiyama, H., Natsume, T., Shimasaki, S., Sugino, H., & Ueno, N. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.16.9337 · Cited by 450 · see citing works
The metabolic actions of glucagon revisited
Habegger, K. M., Heppner, K. M., Geary, N., Bartness, T. J., DiMarchi, R., & Tschöp, M. H. (2010) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2010.187 · Cited by 406 · see citing works
Follistatin complexes Myostatin and antagonises Myostatin-mediated inhibition of myogenesis
Amthor, H., Nicholas, G., McKinnell, I., Kemp, C. F., Sharma, M., Kambadur, R., & Patel, K. (2004) · Developmental Biology · doi:10.1016/j.ydbio.2004.01.046 · Cited by 401 · see citing works
Physiologic action of glucagon on liver glucose metabolism
Ramnanan, C. J., Edgerton, D. S., Kraft, G., & Cherrington, A. D. (2011) · Diabetes Obesity and Metabolism · doi:10.1111/j.1463-1326.2011.01454.x · Cited by 293 · see citing works
Jones, K. L., Mansell, A. S., Patella, S., Scott, B. J., Hedger, M. P., de Kretser, D., & Phillips, D. J. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0705971104 · Cited by 280 · see citing works
Metabolic Regulation: A Human Perspective
Frayn, K. N. (1996) · Cited by 276 · see citing works
Fibroblast Growth Factor 21 Mediates Specific Glucagon Actions
Habegger, K. M., Stemmer, K., Cheng, C., Müller, T. D., Heppner, K. M., Ottaway, N., Holland, J., Hembree, J. L., Smiley, D., Gelfanov, V., et al. (2013) · Diabetes · doi:10.2337/db12-1116 · Cited by 245 · see citing works
Primary structure of the human follistatin precursor and its genomic organization
Shimasaki, S., Koga, M., Esch, F., Cooksey, K., Mercado, M., Koba, A., Ueno, N., Ying, S. Y., Ling, N., & Guillemin, R. (1988) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.85.12.4218 · Cited by 232 · see citing works
Liver-Specific Disruption of the Murine Glucagon Receptor Produces α-Cell Hyperplasia
Longuet, C., Robledo, A. M., Dean, E. D., Dai, C., Ali, S., McGuinness, I., de Chavez, V., Vuguin, P. M., Charron, M. J., Powers, A. C., et al. (2012) · Diabetes · doi:10.2337/db11-1605 · Cited by 207 · see citing works
Hansen, J., Brandt, C., Nielsen, A. R., Hojman, P., Whitham, M., Febbraio, M. A., Pedersen, B. K., & Plomgaard, P. (2011) · Endocrinology · doi:10.1210/en.2010-0868 · Cited by 200 · see citing works
Self-citationMetabolic Regulation: A Human Perspective
Ljungqvist, O. H. (2010) · Clinical Nutrition · doi:10.1016/j.clnu.2010.12.002 · Cited by 189 · see citing works
Autocrine/paracrine regulation of pituitary function by activin, inhibin and follistatin
Bilezikjian, L. M., Blount, A. L., Leal, A. M. O., Donaldson, C., Fischer, W. H., & Vale, W. (2004) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2004.02.010 · Cited by 170 · see citing works
Structural basis for the inhibition of activin signalling by follistatin
Harrington, A. E., Morris-Triggs, S. A., Ruotolo, B. T., Robinson, C. V., Ohnuma, S., & Hyvönen, M. (2006) · The EMBO Journal · doi:10.1038/sj.emboj.7601000 · Cited by 166 · see citing works
Hedger, M. P., & de Kretser, D. M. (2013) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2013.03.003 · Cited by 138 · see citing works
Liver-derived systemic factors drive β cell hyperplasia in insulin-resistant states
El Ouaamari, A., Kawamori, D., Dirice, E., Liew, C. W., Shadrach, J. L., Hu, J., Katsuta, H., Hollister-Lock, J., Qian, W.-J., Wagers, A. J., et al. (2013) · Cell Reports · doi:10.1016/j.celrep.2013.01.007 · Cited by 136 · see citing works
Fat Metabolism During Exercise: A Review. Part I: Fatty Acid Mobilization and Muscle Metabolism
Jeukendrup, A. E., Saris, W. H. M., & Wagenmakers, A. J. M. (1998) · International Journal of Sports Medicine · doi:10.1055/s-2007-971911 · Cited by 124 · see citing works
Nguyen, T. H., Oberholzer, J., Birraux, J., Majno, P. E., Morel, P., & Trono, D. (2002) · Molecular Therapy · doi:10.1006/mthe.2002.0653 · Cited by 124 · 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
Self-citationBouzakri, K., Plomgaard, P., Berney, T., Donath, M. Y., Pedersen, B. K., & Halban, P. A. (2011) · Diabetes · doi:10.2337/db10-1178 · Cited by 122 · see citing works
Self-citationRouiller, D., Cirulli, V., & Halban, P. (1991) · Developmental Biology · doi:10.1016/0012-1606(91)90332-w · Cited by 98 · see citing works
Self-citationSkak, C., & Keiding, S. (1987) · Liver International · doi:10.1111/j.1600-0676.1987.tb00336.x · Cited by 94 · see citing works
Arafat, A. M., Kaczmarek, P., Skrzypski, M., Pruszyńska‐Oszmałek, E., Kolodziejski, P. A., Szczepankiewicz, D., Sassek, M., Wojciechowicz, T., Wiedenmann, B. J., Pfeiffer, A. F. H., et al. (2012) · Diabetologia · doi:10.1007/s00125-012-2803-y · Cited by 90 · see citing works
The effects of prolonged fasting on plasma triglyceride kinetics in man
Streja, D. A., Marliss, E. B., & Steiner, G. A. (1977) · Metabolism · doi:10.1016/0026-0495(77)90094-4 · Cited by 82 · see citing works
Krogh‐Madsen, R., Plomgaard, P., Akerstrom, T. C. A., Møller, K., Schmitz, O., & Pedersen, B. K. (2007) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00507.2007 · Cited by 78 · see citing works
Self-citationA complex role of activin A in non-alcoholic fatty liver disease
Yndestad, A., Haukeland, J. W., Dahl, T. B., Bjøro, K., Gladhaug, I. P., Berge, C., Damås, J. K., Haaland, T., Løberg, E. M., Linnestad, P., et al. (2009) · The American Journal of Gastroenterology · doi:10.1038/ajg.2009.318 · Cited by 75 · see citing works
Hansen, J., Rinnov, A., Krogh‐Madsen, R., Fischer, C. P., Andreasen, A. S., Berg, R. M. G., Møller, K., Pedersen, B. K., & Plomgaard, P. (2013) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.2415 · Cited by 71 · see citing works
Differential distribution of follistatin isoforms: application of a new FS315-specific immunoassay
Schneyer, A. L., Wang, Q., Sidis, Y., & Sluss, P. M. (2004) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2004-0162 · Cited by 71 · see citing works
Mai, G., Huy, N. T., Morel, P., Mei, J., Andrès, A., Bosco, D., Baertschiger, R. M., Toso, C., Berney, T., Majno, P. E., et al. (2005) · Xenotransplantation · doi:10.1111/j.1399-3089.2005.00248.x · Cited by 69 · see citing works
Structural and Biophysical Coupling of Heparin and Activin Binding to Follistatin Isoform Functions
Lerch, T. F., Shimasaki, S., Woodruff, T. K., & Jardetzky, T. S. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m700737200 · Cited by 66 · see citing works
Follistatin: A Novel Therapeutic for the Improvement of Muscle Regeneration
Yaden, B. C., Croy, J. E., Wang, Y., Wilson, J. M., Datta‐Mannan, A., Shetler, P. K., Milner, A., Bryant, H. U., Andrews, J., Dai, G., et al. (2014) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.113.211169 · Cited by 64 · see citing works
Role of Follistatin in Promoting Adipogenesis in Women
Flanagan, J. N., Linder, K., Mejhert, N., Dungner, E., Wåhlén, K., Decaunes, P., Rydén, M., Björklund, P., Arver, S., Bhasin, S., et al. (2009) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2008-2005 · Cited by 63 · see citing works
Immunohistochemical Localization of Follistatin in Rat Tissues.
Satō, K., Ogawa, K., Hayashi, Y., Nakamura, T., Titani, K., & Sugino, H. (1991) · Endocrinologia Japonica · doi:10.1507/endocrj1954.38.383 · Cited by 62 · see citing works
Bouzakri, K., Ribaux, P., & Halban, P. A. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.048058 · Cited by 60 · see citing works
Self-citationFollistatin and follistatin like-3 differentially regulate adiposity and glucose homeostasis
Brown, M. L., Bonomi, L., Ungerleider, N., Zina, J., Kimura, F., Mukherjee, A., Sidis, Y., & Schneyer, A. (2011) · Obesity · doi:10.1038/oby.2011.97 · Cited by 55 · see citing works
Reciprocal modulation of adult beta cell maturity by activin A and follistatin
Szabat, M., Johnson, J. D., & Piret, J. M. (2010) · Diabetologia · doi:10.1007/s00125-010-1758-0 · Cited by 53 · see citing works
Vamvini, M. T., Aronis, K. N., Chamberland, J. P., & Mantzoros, C. S. (2011) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2011-1665 · Cited by 53 · see citing works
Fractalkine (CX3CL1), a new factor protecting β-cells against TNFα
Rütti, S., Arous, C., Schvartz, D., Timper, K., Sanchez, J., Dermitzakis, E. T., Donath, M. Y., Halban, P. A., & Bouzakri, K. (2014) · Molecular Metabolism · doi:10.1016/j.molmet.2014.07.007 · Cited by 40 · see citing works
Self-citationMiyanaga, K., & Shimasaki, S. (1993) · Molecular and Cellular Endocrinology · doi:10.1016/0303-7207(93)90080-4 · Cited by 37 · see citing works
Overcoming Insulin Insufficiency by Forced Follistatin Expression in β -cells of db/db Mice
Zhao, C., Qiao, C., Tang, R., Jiang, J., Li, J., Martin, C. B., Bulaklak, K., Li, J., Wang, D. W., & Xiao, X. (2015) · Molecular Therapy · doi:10.1038/mt.2015.29 · Cited by 37 · see citing works
Regulation of the expression of follistatin in rat hepatocytes
Zhang, Y.-Q., Kanzaki, M., Shibata, H., & Kojima, I. (1997) · Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression · doi:10.1016/s0167-4781(97)00085-7 · Cited by 36 · see citing works
Nakatani, M., Kokubo, M., Ohsawa, Y., Sunada, Y., & Tsuchida, K. (2011) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00430.2010 · Cited by 34 · see citing works
Ungerleider, N., Bonomi, L. M., Brown, M., & Schneyer, A. L. (2013) · Endocrinology · doi:10.1210/en.2012-1844 · Cited by 27 · see citing works
Follistatin complexes Myostatin and antagonises Myostatin-mediated inhibition of myogenesis
Amthor, H. (2004) · Developmental Biology · doi:10.1016/s0012-1606(04)00118-6 · Cited by 25 · see citing works
Activin A Decreases glucagon and arx Gene Expression in α-Cell Lines
Mamin, A., & Philippé, J. (2006) · Molecular Endocrinology · doi:10.1210/me.2005-0530 · Cited by 21 · see citing works
Glucagon receptors in endothelial and Kupffer cells of mouse liver.
Watanabe, J., Kanai, K., & Kanamura, S. (1988) · Journal of Histochemistry & Cytochemistry · doi:10.1177/36.9.2841370 · Cited by 19 · see citing works
Liu, H., Wang, J., Yu, H., Zhang, R., Chen, X., Jin, H., Dai, F., Li, L., & Xu, F. (2012) · Applied Microbiology and Biotechnology · doi:10.1007/s00253-012-3908-4 · Cited by 11 · see citing works
Effect of sodium fluoride on cyclic AMP production in rat hepatocytes.
Shahed, A. R., Miller, A., Chalker, D., et al. (1979) · PubMed · Cited by 9 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Muscle–Organ Crosstalk: The Emerging Roles of Myokines
Severinsen, M. C. K., & Pedersen, B. K. (2020) · Endocrine Reviews · doi:10.1210/endrev/bnaa016 · Cited by 1,226 · see citing works
“The Fibroblast growth factor 21 (FGF-21) (150) and Follistatin (151) are released from human liver during exercise and this release is controlled by the glucagon-to-insulin ratio (152).”
BackgroundSelf-citationGonzalez-Gil, A. M., & Elizondo-Montemayor, L. (2020) · Nutrients · doi:10.3390/nu12061899 · Cited by 278 · 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
Adipokines, Myokines, and Hepatokines: Crosstalk and Metabolic Repercussions
de Oliveira dos Santos, A. R., de Oliveira Zanuso, B., Miola, V. F. B., Barbalho, S. M., Santos Bueno, P. C., Flato, U. A. P., Detregiachi, C. R. P., Buchaim, D. V., Buchaim, R. L., Tofano, R. J., et al. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22052639 · Cited by 189 · see citing works
Stefanakis, K., Kokkorakis, M., & Mantzoros, C. S. (2024) · Metabolism · doi:10.1016/j.metabol.2024.156057 · Cited by 142 · 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
Self-citationInactivating hepatic follistatin alleviates hyperglycemia
Tao, R., Wang, C., Stöhr, O., Qiu, W., Hu, Y., Miao, J., Dong, X. C., Leng, S., Stefater, M., Stylopoulos, N., et al. (2018) · Nature Medicine · doi:10.1038/s41591-018-0048-0 · Cited by 104 · see citing works
Gong, M. M., Lugo-Cintron, K. M., White, B. R., Kerr, S. C., Harari, P. M., & Beebe, D. J. (2019) · Biomaterials · doi:10.1016/j.biomaterials.2019.119225 · Cited by 87 · see citing works
The Role of the Skeletal Muscle Secretome in Mediating Endurance and Resistance Training Adaptations
Leuchtmann, A. B., Adak, V., Dilbaz, S., & Handschin, C. (2021) · Frontiers in Physiology · doi:10.3389/fphys.2021.709807 · Cited by 84 · see citing works
Effect of Various Exercise Regimens on Selected Exercise-Induced Cytokines in Healthy People
Domin, R., Dadej, D., Pytka, M., Zybek-Kocik, A., Ruchała, M., & Guzik, P. (2021) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph18031261 · Cited by 79 · see citing works
“8 years (n = 10) Blood samples for analysis of hormones were obtained before a test and then every hour (one extra sample 30 min post-exercise) simultaneously from the hepatic vein and the brachial artery 5-fold increase in plasma FST in the hepatic vein and brachial artery during the first 2 h of recovery [43]”
BackgroundMethodInfluentialAltered Myokine Secretion Is an Intrinsic Property of Skeletal Muscle in Type 2 Diabetes
Ciaraldi, T. P., Ryan, A. J., Mudaliar, S. R., & Henry, R. R. (2016) · PLOS ONE · doi:10.1371/journal.pone.0158209 · Cited by 66 · see citing works
Circulating follistatin in relation to energy metabolism
Hansen, J. S., & Plomgaard, P. (2016) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2016.06.002 · Cited by 62 · see citing works
Self-citationIngerslev, B., Hansen, J. S., Hoffmann, C., Clemmesen, J. O., Secher, N. H., Scheler, M., Hrabĕ de Angelis, M., Häring, H. U., Pedersen, B. K., Weigert, C., et al. (2017) · Molecular Metabolism · doi:10.1016/j.molmet.2017.06.018 · Cited by 61 · see citing works
Hepatokines—A novel group of exercise factors
Weigert, C., Hoene, M., & Plomgaard, P. (2019) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-018-2216-y · Cited by 57 · see citing works
Self-citationThe hepatokine Tsukushi is released in response to NAFLD and impacts cholesterol homeostasis
Mouchiroud, M., Camiré, É., Aldow, M., Caron, A., Jubinville, É., Turcotte, L., Kaci, I., Beaulieu, M.-J., Roy, C., Labbé, S. M., et al. (2019) · JCI Insight · doi:10.1172/jci.insight.129492 · Cited by 57 · see citing works
Sargeant, J. A., Aithal, G. P., Takamura, T., Misu, H., Takayama, H., Douglas, J. A., Turner, M. C., Stensel, D. J., Nimmo, M. A., Webb, D. R., et al. (2018) · Applied Physiology, Nutrition, and Metabolism · doi:10.1139/apnm-2017-0639 · Cited by 56 · see citing works
Role of exercise-induced hepatokines in metabolic disorders
Ennequin, G., Sirvent, P., & Whitham, M. (2019) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00433.2018 · Cited by 54 · see citing works
Dantas, W. S., Roschel, H., Murai, I. H., Gil, S., Davuluri, G., Axelrod, C. L., Ghosh, S., Newman, S. S., Zhang, H., Shinjo, S. K., et al. (2020) · Diabetes · doi:10.2337/db19-1180 · Cited by 54 · see citing works
Perakakis, N., Mougios, V., Fatouros, I., Siopi, A., Draganidis, D., Peradze, N., Ghaly, W., & Mantzoros, C. S. (2018) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2018-01056 · Cited by 52 · see citing works
Do diabetes and obesity affect the metabolic response to exercise?
Plomgaard, P., & Weigert, C. (2017) · Current Opinion in Clinical Nutrition & Metabolic Care · doi:10.1097/mco.0000000000000379 · Cited by 10 · see citing works
Self-citation
- Authors
- Hansen, J. S., Rutti, S., Arous, C., Clemmesen, J. O., Secher, N. H., Drescher, A., Gonelle-Gispert, C., Halban, P. A., Pedersen, B. K., Weigert, C., Bouzakri, K., & Plomgaard, P.
- Affiliations
- University of Geneva (CH)
- Corresponding author
- Plomgaard, Peter
- ORCID
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2016-02
- Volume
- 101
- Issue
- 2
- Pages
- 550-560
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2193288511
- Cited by
- 125
- References
- 51
- Citations by year
- 2026: 9 · 2025: 12 · 2024: 15 · 2023: 16 · 2022: 12 · 2021: 11 · 2020: 12 · 2019: 11 · 2018: 12 · 2017: 7 · 2016: 7 · 2015: 1
- FWCI
- 9.06
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, other-oa)
- HAL (submittedVersion)
- Site cant be reached (submittedVersion)
- PuSH - Publication Server of Helmholtz Zentrum München (submittedVersion)
- Funders
- National Research Foundation
- Deutsche Forschungsgemeinschaft
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- Danmarks Grundforskningsfond (09-067009, DNRF55, 09-075724)
- Rigshospitalet
- Region Hovedstaden (DNRF55)
- TrygFonden
- Schweizerischen Gesellschaft für Endokrinologie und Diabetologie
- Center for Strategic Research
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fibroblast Growth Factor Research
- Keywords
- follistatin, liver, physical activity, hepatic secretion, cAMP signaling, hepatocytes, pancreatic islets, beta-cell apoptosis, beta-cell proliferation, negative energy balance, hormone signaling
- MeSH terms
- Cyclic AMP, Animals, Cell Survival, Cells, Cultured, Emulsions, Glucagon, Humans, Insulin, Islets of Langerhans, Liver, Male, Phospholipids, Soybean Oil, Exercise, Hepatocytes, Follistatin, Cell Line, Tumor, Cell Proliferation, Insulin-Secreting Cells, Rats, Young Adult
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
