The Glucagon Receptor Is Required for the Adaptive Metabolic Response to Fasting
Open accessAbstract
Glucagon receptor (Gcgr) signaling maintains hepatic glucose production during the fasting state; however, the importance of the Gcgr for lipid metabolism is unclear. We show here that fasted Gcgr-/- mice exhibit a significant increase in hepatic triglyceride secretion and fasting increases fatty acid oxidation (FAO) in wild-type (WT) but not in Gcgr-/- mice. Moreover fasting upregulated the expression of FAO-related hepatic mRNA transcripts in Gcgr+/+ but not in Gcgr-/- mice. Exogenous glucagon administration reduced plasma triglycerides in WT mice, inhibited TG synthesis and secretion, and stimulated FA beta oxidation in Gcgr+/+ hepatocytes. The actions of glucagon on TG synthesis and FAO were abolished in PPARalpha-/- hepatocytes. These findings demonstrate that the Gcgr receptor is required for control of lipid metabolism during the adaptive metabolic response to fasting.
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Activation of the glucagon receptor may have a favorable effect on the development and treatment of MAFLD, commonly seen in T2DM.
“Based on these findings, activation of the glucagon receptor may have a favorable effect on the development and treatment of MAFLD, commonly seen in T2DM.”
From New Developments in Pharmacological Treatment of Obesity and Type 2 Diabetes—Beyond and within GLP-1 Receptor Agonists (2024) · cites this paper as [66]
The Discussion (page not available) reports that glucagon-receptor signaling enhances fatty-acid oxidation and that receptor-deficient mice rapidly develop hepatic steatosis after high-fat feeding. This supports a possible protective role against fatty liver, but the paper does not establish that receptor activation prevents or treats MAFLD in people with T2DM; it also notes that reducing receptor activity lowered liver triglycerides in some diabetic rodents. (LLM, conf=0.85)
Experimental — accuracy not yet measuredIn addition to its blood glucose-increasing effect, glucagon activates fat breakdown and inhibits lipogenesis in the liver, reducing concentrations of non-esterified fatty acids and triacylglycerol, and moderating triglyceride content in liver cells in animal experiments.
“In addition to its blood glucose-increasing effect, glucagon activates fat breakdown and inhibits lipogenesis in the liver, reducing concentrations of non-esterified fatty acids and triacylglycerol, and moderating triglyceride content in liver cells in animal experiments [66].”
From New Developments in Pharmacological Treatment of Obesity and Type 2 Diabetes—Beyond and within GLP-1 Receptor Agonists (2024) · cites this paper as [66]
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Cites
Peroxisome proliferator–activated receptor α mediates the adaptive response to fasting
Kersten, S., Seydoux, J., Peters, J. M., Gonzalez, F. J., Desvergne, B., & Wahli, W. (1999) · Journal of Clinical Investigation · doi:10.1172/jci6223 · Cited by 1,649 · see citing works
Inagaki, T., Dutchak, P., Zhao, G., Ding, X., Gautron, L., Parameswara, V., Li, Y., Goetz, R., Mohammadi, M., Esser, V., et al. (2007) · Cell Metabolism · doi:10.1016/j.cmet.2007.05.003 · Cited by 1,504 · 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
The CREB coactivator TORC2 is a key regulator of fasting glucose metabolism
Koo, S., Flechner, L., Qi, L., Zhang, X., Screaton, R. A., Jeffries, S., Hedrick, S. A., Xu, W., Boussouar, F., Brindle, P. K., et al. (2005) · Nature · doi:10.1038/nature03967 · Cited by 993 · see citing works
Sorting out the roles of PPAR in energy metabolism and vascular homeostasis
Lefebvre, P. (2006) · Journal of Clinical Investigation · doi:10.1172/jci27989 · Cited by 962 · see citing works
Glucagon and regulation of glucose metabolism
Jiang, G., & Zhang, B. B. (2003) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00492.2002 · Cited by 905 · see citing works
Gelling, R. W., Du, X. Q., Dichmann, D. S., Rømer, J., Huang, H., Cui, L., Obici, S., Tang, B., Holst, J. J., Fledelius, C., et al. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0237106100 · Cited by 563 · see citing works
Self-citationADD1/SREBP-1c Is Required in the Activation of Hepatic Lipogenic Gene Expression by Glucose
Foretz, M., Pacot, C., Dugail, I., Lemarchand, P., Guichard, C., Lièpvre, X. L., Lubrano-Berthelier, C., Spiegelman, B. M., Kim, J. B., Ferré, P., et al. (1999) · Molecular and Cellular Biology · doi:10.1128/mcb.19.5.3760 · Cited by 548 · see citing works
International Union of Pharmacology. XXXV. The Glucagon Receptor Family
Mayo, K. E., Miller, L. J., BATAILLE, D., Dalle, S., Göke, B., Thorens, B., & Drucker, D. J. (2003) · Pharmacological Reviews · doi:10.1124/pr.55.1.6 · Cited by 507 · see citing works
Self-citationExpression cloning and signaling properties of the rat glucagon receptor
Jelinek, L., Lok, S., Rosenberg, G., Smith, R., Grant, F., BIGGS, S., Bensch, P., Kuijper, J. L., Sheppard, P. O., Sprecher, C. A., et al. (1993) · Science · doi:10.1126/science.8384375 · Cited by 397 · see citing works
Activation of two signal-transduction systems in hepatocytes by glucagon
Wakelam, M. J. O., Murphy, G. J., Hruby, V. J., & Houslay, M. D. (1986) · Nature · doi:10.1038/323068a0 · Cited by 389 · see citing works
Patsouris, D., Reddy, J. K., Müller, M. M., & Kersten, S. (2005) · Endocrinology · doi:10.1210/en.2005-1132 · Cited by 339 · see citing works
CREB controls hepatic lipid metabolism through nuclear hormone receptor PPAR-γ
Herzig, S., Hedrick, S. A., Morantte, I. G., Koo, S., Galimi, F., & Montminy, M. (2003) · Nature · doi:10.1038/nature02110 · Cited by 321 · see citing works
Otway, S., & Robinson, D. S. (1967) · The Journal of Physiology · doi:10.1113/jphysiol.1967.sp008211 · Cited by 288 · see citing works
Glucagon physiology and pathophysiology
Sherwood, L. M., Parris, E. E., & Unger, R. H. (1971) · New England Journal of Medicine · doi:10.1056/nejm197108192850806 · Cited by 267 · see citing works
Conarello, S. L., Jiang, G., Mu, J., Li, Z., Woods, J., Zycband, E., Ronan, J., Liu, F., Roy, R. S., Zhu, L., et al. (2006) · Diabetologia · doi:10.1007/s00125-006-0481-3 · Cited by 224 · see citing works
Self-citationSloop, K. W., Cao, J. X. C., Siesky, A. M., Zhang, H. Y., Bodenmiller, D. M., Cox, A. L., Jacobs, S. J., Moyers, J. S., Owens, R. A., Showalter, A. D., et al. (2004) · Journal of Clinical Investigation · doi:10.1172/jci20911 · Cited by 219 · see citing works
Liang, Y. T., Osborne, M. C., Monia, B. P., Bhanot, S., Gaarde, W. A., Reed, C. A., She, P., Jetton, T. L., & Demarest, K. T. (2004) · Diabetes · doi:10.2337/diabetes.53.2.410 · Cited by 203 · see citing works
Hyperglucagonemia and Its Suppression
Raskin, P., & Unger, R. H. (1978) · New England Journal of Medicine · doi:10.1056/nejm197808312990901 · Cited by 197 · see citing works
Hyperglycemia of Diabetic Rats Decreased by a Glucagon Receptor Antagonist
Johnson, D. G., Goebel, C. U., Hruby, V. J., Bregman, M. D., & Trivedi, D. B. (1982) · Science · doi:10.1126/science.6278587 · Cited by 166 · see citing works
Flock, G. B., Baggio, L. L., Longuet, C., & Drucker, D. J. (2007) · Diabetes · doi:10.2337/db07-0697 · Cited by 164 · see citing works
Self-citationp38 Mitogen-activated Protein Kinase Plays a Stimulatory Role in Hepatic Gluconeogenesis
Cao, W., Collins, Q. F., Becker, T. C., Robidoux, J., Lupo, E. G., Xiong, Y., Daniel, K. W., Floering, L. M., & Collins, S. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m506223200 · Cited by 146 · see citing works
Kimball, S. R., Siegfried, B. A., & Jefferson, L. S. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m410755200 · Cited by 133 · see citing works
Factors affecting lipoprotein metabolism.
Scanu, A. M. (1965) · PubMed · Cited by 133 · see citing works
Biological activities of des-His1[Glu9]glucagon amide, a glucagon antagonist
Unson, C. G., Gurzenda, E. M., & Merrifield, R. B. (1989) · Peptides · doi:10.1016/0196-9781(89)90010-7 · Cited by 119 · see citing works
Sumanasekera, W. K., Tien, E. S., Turpey, R., Heuvel, J. P. V., & Perdew, G. H. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m211261200 · Cited by 108 · see citing works
Jianping, C. H. E. N., Ishac, E. J. N., Dent, P., Kunos, G., & Gao, B. (1998) · Biochemical Journal · doi:10.1042/bj3340669 · Cited by 107 · see citing works
Scanu, A. M. (1965) · Advances in lipid research · doi:10.1016/b978-1-4831-9939-9.50009-7 · Cited by 99 · see citing works
p38 Mitogen-activated Protein Kinase Plays an Inhibitory Role in Hepatic Lipogenesis
Xiong, Y., Collins, Q. F., An, J., Lupo, E. G., Liu, H. Y., Liu, D., Robidoux, J., Liu, Z., & Cao, W. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m606742200 · Cited by 93 · see citing works
Hypolipemic action of glucagon in experimental endogenous lipemia in the rat
Eaton, R. P. (1973) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)36889-9 · Cited by 86 · see citing works
Zhang, B., Marcus, S. L., Miyata, K., Subramani, S. E., Capone, J. P., & Rachubinski, R. A. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)31476-5 · Cited by 79 · see citing works
Sumanasekera, W. K., Tien, E. S., Davis, J. W., Turpey, R., Perdew, G. H., & Heuvel, J. P. V. (2003) · Biochemistry · doi:10.1021/bi0347353 · Cited by 78 · see citing works
Prip‐Buus, C., Pégorier, J. P., Duée, P., Kohl, C., & Girard, J. R. (1990) · Biochemical Journal · doi:10.1042/bj2690409 · Cited by 73 · see citing works
Giordano, A., Calvani, M., Petillo, O., Grippo, P., Tuccillo, F. M., Melone, M. A. B., Bonelli, P., Calarco, A., & Peluso, G. (2005) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4401636 · Cited by 65 · see citing works
Glucagon activates Ca2+ and Cl− channels in rat hepatocytes
Aromataris, E., Roberts, M. L., Barritt, G. J., & Rychkov, G. Y. (2006) · The Journal of Physiology · doi:10.1113/jphysiol.2006.109819 · Cited by 62 · see citing works
Koehler, J. A., & Drucker, D. J. (2006) · Diabetes · doi:10.2337/db05-1145 · Cited by 60 · see citing works
Self-citationPrevention of Fatty Liver in Transition Dairy Cows by Subcutaneous Injections of Glucagon
Nafikov, R. A., Ametaj, B. N., Bobe, G., Koehler, K. J., Young, J. W., & Beitz, D. C. (2006) · Journal of Dairy Science · doi:10.3168/jds.s0022-0302(06)72221-4 · Cited by 50 · see citing works
Hiyoshi, H., Yanagimachi, M., Ito, M., Yasuda, N., Okada, T., Ikuta, H., Shinmyo, D., Tanaka, K., Kurusu, N., Yoshida, I., et al. (2003) · Journal of Lipid Research · doi:10.1194/jlr.m200316-jlr200 · Cited by 47 · see citing works
Effects of Exogenous Glucagon on Lipids in Lipoproteins and Liver of Lactating Dairy Cows
Bobe, G., Ametaj, B. N., Young, J. W., & Beitz, D. C. (2003) · Journal of Dairy Science · doi:10.3168/jds.s0022-0302(03)73886-7 · Cited by 42 · see citing works
Charbonneau, A., Couturier, K., Gauthier, M., & Lavoie, J.-M. (2005) · International Journal of Sports Medicine · doi:10.1055/s-2004-821225 · Cited by 40 · see citing works
Effects of chronic glucagon administration on cholesterol and bile acid metabolism
Guettet, C., Mathé, D., Riottot, M., & Lutton, C. (1988) · Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism · doi:10.1016/0005-2760(88)90283-4 · Cited by 36 · see citing works
Potential Treatment of Fatty Liver with 14-Day Subcutaneous Injections of Glucagon
Bobe, G., Ametaj, B. N., Young, J. W., & Beitz, D. C. (2003) · Journal of Dairy Science · doi:10.3168/jds.s0022-0302(03)73915-0 · Cited by 36 · see citing works
Effects of chronic glucagon administration on rat lipoprotein composition
Guettet, C., Mathé, D., Navarro, N., & Lecuyer, B. (1989) · Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism · doi:10.1016/0005-2760(89)90042-8 · Cited by 33 · see citing works
Guettet, C., Rostaqui, N., Mathé, D., Lécuyer, B., Navarro, N., & JACOTOT, B. (1991) · Lipids · doi:10.1007/bf02536072 · Cited by 29 · see citing works
Charbonneau, A., Melançon, A., Lavoie, C., & Lavoie, J.-M. (2005) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00570.2004 · Cited by 27 · see citing works
Rodrı́guez, C., Noé, V., Cabrero, À., Ciudad, C. J., & Laguna, J. C. (2000) · Molecular Pharmacology · doi:10.1124/mol.58.1.185 · Cited by 22 · see citing works
Bobe, G., Ametaj, B. N., Young, J. W., Anderson, L. L., & Beitz, D. C. (2006) · Animal Reproduction Science · doi:10.1016/j.anireprosci.2006.11.003 · Cited by 10 · see citing works
Flagged first, then by citations
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Energy Metabolism in the Liver
Rui, L. (2014) · Comprehensive physiology · doi:10.1002/cphy.c130024 · Cited by 2,258 · see citing works
Regulation of hepatic glucose metabolism in health and disease
Petersen, M. C., Vatner, D. F., & Shulman, G. I. (2017) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2017.80 · Cited by 1,131 · see citing works
Metabolism disrupting chemicals and metabolic disorders
Heindel, J. J., Blumberg, B., Cave, M., Machtinger, R., Mantovani, A., Mendez, M. A., Nadal, A., Palanza, P., Panzica, G., Sargis, R., et al. (2017) · Reproductive Toxicology · doi:10.1016/j.reprotox.2016.10.001 · Cited by 1,101 · see citing works
Mechanisms of hepatic triglyceride accumulation in non-alcoholic fatty liver disease
Kawano, Y., & Cohen, D. E. (2013) · Journal of Gastroenterology · doi:10.1007/s00535-013-0758-5 · Cited by 968 · see citing works
Potthoff, M. J., Inagaki, T., Satapati, S., Ding, X., He, T., Goetz, R., Mohammadi, M., Finck, B. N., Mangelsdorf, D. J., Kliewer, S. A., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0904187106 · Cited by 704 · see citing works
Glucagonocentric restructuring of diabetes: A pathophysiologic and therapeutic makeover
Unger, R. H., & Cherrington, A. D. (2012) · Journal of Clinical Investigation · doi:10.1172/jci60016 · Cited by 670 · see citing works
GLP-1 physiology informs the pharmacotherapy of obesity
Drucker, D. J. (2022) · Molecular Metabolism · doi:10.1016/j.molmet.2021.101351 · Cited by 510 · see citing works
Self-citationPhysiology of Proglucagon Peptides: Role of Glucagon and GLP-1 in Health and Disease
Sandoval, D. A., & D'Alessio, D. A. (2015) · Physiological Reviews · doi:10.1152/physrev.00013.2014 · Cited by 498 · 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
Glucagon-Like Peptide 1/Glucagon Receptor Dual Agonism Reverses Obesity in Mice
Pocai, A., Carrington, P. E., Adams, J. R., Wright, M., Eiermann, G., Zhu, L., Du, X., Petrov, A., Lassman, M. E., Jiang, G., et al. (2009) · Diabetes · doi:10.2337/db09-0278 · Cited by 409 · see citing works
Distinct but complementary contributions of PPAR isotypes to energy homeostasis
Dubois, V., Eeckhoute, J., Lefèbvre, P., & Staels, B. (2017) · Journal of Clinical Investigation · doi:10.1172/jci88894 · Cited by 385 · see citing works
Efficacy and Safety of GLP-1 Medicines for Type 2 Diabetes and Obesity
Drucker, D. J. (2024) · Diabetes Care · doi:10.2337/dci24-0003 · Cited by 383 · see citing works
Self-citationEnergy Metabolism in the Liver
Rui, L. (2014) · Comprehensive physiology · doi:10.1002/j.2040-4603.2014.tb00548.x · Cited by 382 · see citing works
Role of Mitochondria in Nonalcoholic Fatty Liver Disease
Nassir, F., & Ibdah, J. A. (2014) · International Journal of Molecular Sciences · doi:10.3390/ijms15058713 · Cited by 359 · see citing works
Glucagon-like peptide-1 receptor co-agonists for treating metabolic disease.
Baggio, L. L., & Drucker, D. J. (2021) · Molecular Metabolism · doi:10.1016/j.molmet.2020.101090 · Cited by 299 · see citing works
Self-citationHsieh, J., Longuet, C., Baker, C. L., Qin, B., Federico, L. M., Drucker, D. J., & Adeli, K. (2009) · Diabetologia · doi:10.1007/s00125-009-1611-5 · Cited by 276 · see citing works
Self-citationIslet α cells and glucagon--critical regulators of energy homeostasis
Campbell, J. E., & Drucker, D. J. (2015) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2015.51 · Cited by 266 · see citing works
Self-citationThe role of dysregulated glucagon secretion in type 2 diabetes
D'Alessio, D. (2011) · Diabetes, Obesity and Metabolism · doi:10.1111/j.1463-1326.2011.01449.x · Cited by 238 · 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
Glucagon Receptor Signaling and Lipid Metabolism
Galsgaard, K. D., Pedersen, J., Knop, F. K., Holst, J. J., & Wewer Albrechtsen, N. J. (2019) · Frontiers in Physiology · doi:10.3389/fphys.2019.00413 · Cited by 218 · see citing works
Structure of the full-length glucagon class B G-protein-coupled receptor
Zhang, H., Qiao, A., Yang, D., Yang, L., Dai, A., de Graaf, C., Reedtz‐Runge, S., Dharmarajan, V., Zhang, H., Han, G. W., et al. (2017) · Nature · doi:10.1038/nature22363 · Cited by 212 · see citing works
Dean, E. D., Li, M., Prasad, N., Wisniewski, S., Deylen, A. V., Spaeth, J. M., Maddison, L. A., Botros, A., Sedgeman, L. R., Bozadjieva-Kramer, N., et al. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.05.011 · Cited by 207 · see citing works
Brereton, M. F., Vergari, E., Zhang, Q., & Clark, A. (2015) · Journal of Histochemistry & Cytochemistry · doi:10.1369/0022155415583535 · Cited by 206 · see citing works
Glucagon Receptor Signaling and Glucagon Resistance
Janah, L., Kjeldsen, S. A. S., Galsgaard, K. D., Winther‐Sørensen, M., Stojanovska, E., Pedersen, J., Knop, F. K., Holst, J. J., & Albrechtsen, N. J. W. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20133314 · Cited by 205 · see citing works
Glucagon and Amino Acids Are Linked in a Mutual Feedback Cycle: The Liver–α-Cell Axis
Holst, J. J., Wewer Albrechtsen, N. J., Pedersen, J., & Knop, F. K. (2017) · Diabetes · doi:10.2337/db16-0994 · Cited by 187 · see citing works
Glucagon-like Peptide-1 Receptor-based Therapeutics for Metabolic Liver Disease
Yabut, J. M., & Drucker, D. J. (2022) · Endocrine Reviews · doi:10.1210/endrev/bnac018 · Cited by 180 · see citing works
Self-citationMoffett, J. R., Puthillathu, N., Vengilote, R., Jaworski, D. M., & Namboodiri, A. M. A. (2020) · Frontiers in Physiology · doi:10.3389/fphys.2020.580167 · Cited by 182 · see citing works
Guzman, C. B., Zhang, X. M., Liu, R., Regev, A., Shankar, S., Garhyan, P., Pillai, S. G., Kazda, C., Chalasani, N., & Hardy, T. A. (2017) · Diabetes, Obesity and Metabolism · doi:10.1111/dom.12958 · Cited by 172 · see citing works
The Role of Glucagon in the Pathophysiology and Treatment of Type 2 Diabetes
Hædersdal, S., Lund, A., Knop, F. K., & Vilsbøll, T. (2018) · Mayo Clinic Proceedings · doi:10.1016/j.mayocp.2017.12.003 · Cited by 162 · see citing works
Cyphert, H. A., Ge, X., Kohan, A. B., Salati, L. M., Zhang, Y., & Hillgartner, F. B. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.375907 · Cited by 162 · see citing works
Revisiting the role of glucagon in health, diabetes mellitus and other metabolic diseases
Hædersdal, S., Andersen, A., Knop, F. K., & Vilsbøll, T. (2023) · Nature Reviews Endocrinology · doi:10.1038/s41574-023-00817-4 · Cited by 164 · see citing works
The Liver–α-Cell Axis and Type 2 Diabetes
Albrechtsen, N. J. W., Pedersen, J., Galsgaard, K. D., Winther‐Sørensen, M., Suppli, M. P., Janah, L., Gromada, J., Vilstrup, H., Knop, F. K., & Holst, J. J. (2019) · Endocrine Reviews · doi:10.1210/er.2018-00251 · Cited by 149 · see citing works
High protein intake reduces intrahepatocellular lipid deposition in humans
Bortolotti, M., Kreis, R., Debard, C., Cariou, B., Faeh, D., Chetiveaux, M., Ith, M., Vermathen, P., Stefanoni, N., Lê, K.-A., et al. (2009) · The American Journal of Clinical Nutrition · doi:10.3945/ajcn.2008.27296 · Cited by 146 · see citing works
Targeting the glucagon receptor family for diabetes and obesity therapy
Cho, Y. M., Merchant, C. E., & Kieffer, T. J. (2012) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2012.05.009 · Cited by 142 · see citing works
Structure of the glucagon receptor in complex with a glucagon analogue
Zhang, H., Qiao, A., Yang, L., Eps, N. V., Frederiksen, K. S., Yang, D., Dai, A., Cai, X., Zhang, H., Yi, C., et al. (2018) · Nature · doi:10.1038/nature25153 · Cited by 141 · see citing works
Important Hormones Regulating Lipid Metabolism
Zhang, D., Wei, Y., Huang, Q., Chen, Y., Zeng, K., Yang, W., Chen, J., & Chen, J. (2022) · Molecules · doi:10.3390/molecules27207052 · Cited by 143 · see citing works
Dissociating fatty liver and diabetes
Sun, Z., & Lazar, M. A. (2012) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2012.09.005 · Cited by 136 · see citing works
Integrating the inputs that shape pancreatic islet hormone release
Noguchi, G. M., & Huising, M. O. (2019) · Nature Metabolism · doi:10.1038/s42255-019-0148-2 · Cited by 130 · see citing works
Influence of Dietary Macronutrients on Liver Fat Accumulation and Metabolism
Parry, S. A., & Hodson, L. (2017) · Journal of Investigative Medicine · doi:10.1136/jim-2017-000524 · Cited by 131 · see citing works
Kaufman, A., Abuqayyas, L., Denney, W. S., Tillman, E. J., & Rolph, T. (2020) · Cell Reports Medicine · doi:10.1016/j.xcrm.2020.100057 · Cited by 131 · see citing works
Gut-liver interaction in triglyceride-rich lipoprotein metabolism
Xiao, C., Hsieh, J., Adeli, K., & Lewis, G. F. (2011) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00178.2011 · Cited by 126 · see citing works
Hepatic transcriptional responses to fasting and feeding
Bideyan, L., Nagari, R., & Tontonoz, P. (2021) · Genes & Development · doi:10.1101/gad.348340.121 · Cited by 126 · see citing works
Update on the molecular biology of dyslipidemias
Ramasamy, I. (2015) · Clinica Chimica Acta · doi:10.1016/j.cca.2015.10.033 · Cited by 126 · see citing works
Benefits and limitations of reducing glucagon action for the treatment of type 2 diabetes
Ali, S., & Drucker, D. J. (2008) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.90887.2008 · Cited by 124 · see citing works
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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
Repositioning Glucagon Action in the Physiology and Pharmacology of Diabetes
Finan, B., Capozzi, M. E., & Campbell, J. E. (2019) · Diabetes · doi:10.2337/dbi19-0004 · Cited by 117 · see citing works
Metabolic Syndrome and Male Fertility
Martins, A. D., Majzoub, A. A., & Agawal, A. (2018) · The World Journal of Men s Health · doi:10.5534/wjmh.180055 · Cited by 115 · see citing works
Glucagon-Induced Acetylation of Foxa2 Regulates Hepatic Lipid Metabolism
von Meyenn, F., Porstmann, T., Gasser, E., Selevsek, N., Schmidt, A., Aebersold, R. H., & Stoffel, M. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.01.014 · Cited by 114 · see citing works
Kelly, R. P., Garhyan, P., Raddad, E., Fu, H., Lim, C. N., Prince, M. J., Pinaire, J. A., Loh, M. T., & Deeg, M. A. (2015) · Diabetes, Obesity and Metabolism · doi:10.1111/dom.12446 · Cited by 110 · see citing works
Transcriptional and Chromatin Regulation during Fasting – The Genomic Era
Goldstein, I., & Hager, G. L. (2015) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2015.09.005 · Cited by 110 · see citing works
The past, present, and future physiology and pharmacology of glucagon
Capozzi, M. E., D’Alessio, D. A., & Campbell, J. E. (2022) · Cell Metabolism · doi:10.1016/j.cmet.2022.10.001 · Cited by 110 · see citing works
Recent insights into fatty liver, metabolic dyslipidaemia and their links to insulin resistance
Savage, D. B., & Semple, R. K. (2010) · Current Opinion in Lipidology · doi:10.1097/mol.0b013e32833b7782 · Cited by 109 · see citing works
Hepatic energy state is regulated by glucagon receptor signaling in mice
Berglund, E. D., Lee, R. S., Lustig, D. G., Lynes, S. E., Donahue, E. P., Camacho, R. C., Meredith, M. E., Magnuson, M. A., Charron, M. J., & Wasserman, D. H. (2009) · Journal of Clinical Investigation · doi:10.1172/jci38650 · Cited by 106 · see citing works
Self-citationBerger, J. H., Charron, M. J., & Silver, D. L. (2012) · PLoS ONE · doi:10.1371/journal.pone.0050629 · Cited by 105 · see citing works
Self-citationOkamoto, H., Kim, J., Aglione, J., Lee, J., Cavino, K., Na, E., Rafique, A., Kim, J. H., Harp, J., Valenzuela, D. M., et al. (2015) · Endocrinology · doi:10.1210/en.2015-1011 · Cited by 100 · see citing works
Berglund, E. D., Kang, L., Lee, R. S., Hasenour, C. M., Lustig, D. G., Lynes, S. E., Donahue, E. P., Swift, L. L., Charron, M. J., & Wasserman, D. H. (2010) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00263.2010 · Cited by 100 · see citing works
Self-citationRetractedEmerging role of AMP-activated protein kinase in endocrine control of metabolism in the liver
Hasenour, C. M., Berglund, E. D., & Wasserman, D. H. (2012) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2012.06.018 · Cited by 98 · see citing works
Determinants of VLDL-triglycerides production
Nielsen, S., & Karpe, F. (2012) · Current Opinion in Lipidology · doi:10.1097/mol.0b013e3283544956 · Cited by 94 · see citing works
Kim, T., Nason, S., Holleman, C., Pepin, M., Wilson, L., Berryhill, T. F., Wende, A. R., Steele, C., Young, M. E., Barnes, S., et al. (2018) · Diabetes · doi:10.2337/db17-1502 · Cited by 97 · see citing works
Self-citationMechanisms of hepatic fatty acid oxidation and ketogenesis during fasting
Ruppert, P. M. M., & Kersten, S. (2023) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2023.10.002 · Cited by 97 · see citing works
Tschöp, M., Nogueiras, R., & Ahrén, B. (2023) · Diabetologia · doi:10.1007/s00125-023-05929-0 · Cited by 92 · 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
Glucagon Control on Food Intake and Energy Balance
Al–Massadi, O., Fernø, J., Diéguez, C., Nogueiras, R., & Quiñones, M. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20163905 · Cited by 89 · see citing works
Investigational glucagon receptor antagonists in Phase I and II clinical trials for diabetes
Scheen, A. J., Paquot, N., & Lefèbvre, P. J. (2017) · Expert Opinion on Investigational Drugs · doi:10.1080/13543784.2017.1395020 · Cited by 87 · see citing works
The Liver–α-Cell Axis in Health and in Disease
Richter, M. M., Galsgaard, K. D., Elmelund, E., Knop, F. K., Suppli, M. P., Holst, J. J., Winther‐Sørensen, M., Kjeldsen, S. A. S., & Albrechtsen, N. J. W. (2022) · Diabetes · doi:10.2337/dbi22-0004 · Cited by 87 · see citing works
Yang, J., MacDougall, M. L., McDowell, M. T., Xi, L., Wei, R., Zavadoski, W. J., Molloy, M. P., Baker, J. D., Kühn, M., Cabrera, O., et al. (2011) · BMC Genomics · doi:10.1186/1471-2164-12-281 · Cited by 82 · see citing works
Cyphert, H. A., Alonge, K. M., Ippagunta, S. M., & Hillgartner, F. B. (2014) · PLoS ONE · doi:10.1371/journal.pone.0094996 · Cited by 80 · see citing works
Sharma, A. X., Quittner-Strom, E. B., Lee, Y., Johnson, J. A., Martin, S. A., Yu, X., Li, J., Lu, J., Cai, Z. P., Chen, S., et al. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.01.065 · Cited by 72 · see citing works
Insights into the Hexose Liver Metabolism—Glucose versus Fructose
Geidl-Flueck, B., & Gerber, P. (2017) · Nutrients · doi:10.3390/nu9091026 · Cited by 85 · see citing works
Hasenour, 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
Ali, S., Ussher, J. R., Baggio, L. L., Kabir, M. G., Charron, M. J., Ilkayeva, O., Newgard, C. B., & Drucker, D. J. (2014) · Molecular Metabolism · doi:10.1016/j.molmet.2014.11.005 · Cited by 69 · see citing works
Self-citationWatanabe, C., Seino, Y., Miyahira, H., Yamamoto, M., Fukami, A., Ozaki, N., Takagishi, Y., Sato, J., Fukuwatari, T., Shibata, K., et al. (2011) · Diabetes · doi:10.2337/db11-0739 · Cited by 70 · see citing works
Lack of glucagon receptor signaling and its implications beyond glucose homeostasis
Charron, M. J., & Vuguin, P. M. (2015) · Journal of Endocrinology · doi:10.1530/joe-14-0614 · Cited by 68 · see citing works
Self-citationDupont, J., Métayer, S., Ji, B., Ramé, C., Gespach, C. P., Voy, B. H., & Simon, J. (2012) · General and Comparative Endocrinology · doi:10.1016/j.ygcen.2011.12.030 · Cited by 61 · see citing works
Hepatic Glucagon Signaling Regulates PCSK9 and Low-Density Lipoprotein Cholesterol
Spolitu, S., Okamoto, H., Dai, W., Zadroga, J. A., Wittchen, E. S., Gromada, J., & Özcan, L. (2019) · Circulation Research · doi:10.1161/circresaha.118.313648 · Cited by 61 · see citing works
Futile lipid cycling: from biochemistry to physiology
Sharma, A. K., Khandelwal, R., & Wolfrum, C. (2024) · Nature Metabolism · doi:10.1038/s42255-024-01003-0 · Cited by 60 · see citing works
Xiao, C., Pavlic, M., Szeto, L., Patterson, B. W., & Lewis, G. F. (2010) · Diabetes · doi:10.2337/db10-0763 · Cited by 60 · see citing works
Glucagon's Metabolic Action in Health and Disease
Zeigerer, A., Sekar, R., Kleinert, M., Nason, S. R., Habegger, K. M., & Müller, T. D. (2021) · Comprehensive physiology · doi:10.1002/cphy.c200013 · Cited by 76 · see citing works
Hypoxia via ERK Signaling Inhibits Hepatic PPARα to Promote Fatty Liver
Mooli, R. G. R., Rodriguez, J., Takahashi, S., Solanki, S. A., Gonzalez, F. J., Ramakrishnan, S. K., & Shah, Y. M. (2021) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2021.03.011 · Cited by 59 · see citing works
Hepatic glucagon action: beyond glucose mobilization
Kajani, S., Laker, R. C., Ratkova, E. L., Will, S., & Rhodes, C. J. (2024) · Physiological Reviews · doi:10.1152/physrev.00028.2023 · Cited by 60 · see citing works
Pashkov, V., Huang, J., Parameswara, V., Kędzierski, W., Kurrasch, D. M., Tall, G. G., Esser, V., Gerard, R. D., Uyeda, K., Towle, H. C., et al. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.216234 · Cited by 59 · see citing works
Glucagon in artificial pancreas systems: Potential benefits and safety profile of future chronic use
Taleb, N., Haidar, A., Messier, V., Gingras, V., Legault, L., & RABASA-LHORET, R. P. R. (2016) · Diabetes Obesity and Metabolism · doi:10.1111/dom.12789 · Cited by 59 · see citing works
Manell, H., Kristinsson, H., Kullberg, J., Ubhayasekera, S. J. K. A., Mörwald, K., Staaf, J., Cadamuro, J., Zsoldos, F., Göpel, S., Sargsyan, E., et al. (2019) · Pediatric Diabetes · doi:10.1111/pedi.12890 · Cited by 56 · see citing works
Reprogramming of Hepatic Metabolism and Microenvironment in Nonalcoholic Steatohepatitis
Rui, L., & Lin, J. D. (2022) · Annual Review of Nutrition · doi:10.1146/annurev-nutr-062220-105200 · Cited by 56 · see citing works
Hormone-like fibroblast growth factors and metabolic regulation
Long, Y. C., & Kharitonenkov, A. (2011) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2011.04.002 · Cited by 55 · see citing works
Buler, M., Aatsinki, S., Skoumal, R., Komka, Z., Tóth, M., Kerkelä, R., Georgiadi, A., Kersten, S., & Hakkola, J. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.302356 · Cited by 53 · see citing works
Nutrient regulation of glucagon secretion: involvement in metabolism and diabetes
Marroquí, L., Alonso‐Magdalena, P., Merino, B., Fuentes, E., Nadal, Á., & Quesada, I. (2014) · Nutrition Research Reviews · doi:10.1017/s0954422414000031 · Cited by 55 · see citing works
Fougerat, A., Bruse, J., Polizzi, A., Montagner, A., Guillou, H., & Wahli, W. (2024) · Progress in Lipid Research · doi:10.1016/j.plipres.2024.101303 · Cited by 54 · see citing works
Pancreatic endocrine and exocrine signaling and crosstalk in physiological and pathological status
Hu, C., Chen, Y., Yin, X., Xu, R., Yin, C., Wang, C., & Zhao, Y. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-02098-3 · Cited by 59 · see citing works
A Critical Role of Fatty Acid Binding Protein 4 and 5 (FABP4/5) in the Systemic Response to Fasting
Syamsunarno, M. R. A. A., Iso, T., Hanaoka, H., Yamaguchi, A., Obokata, M., Koitabashi, N., Goto, K., Hishiki, T., Nagahata, Y., Matsui, H., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0079386 · Cited by 50 · see citing works
Zhao, F., Zhang, C., Zhou, Q., Hang, K., Zou, X., Chen, Y., Wu, F., Rao, Q., Dai, A., Yin, W., et al. (2021) · eLife · doi:10.7554/elife.68719 · Cited by 49 · see citing works
Wang, M.-Y., Zhang, Z., Zhao, S., Onodera, T., Sun, X.-N., Zhu, Q., Li, C., Li, N., Chen, S., Paredes, M., et al. (2024) · Cell Metabolism · doi:10.1016/j.cmet.2023.12.024 · Cited by 52 · see citing works
Self-citationCrbpI Modulates Glucose Homeostasis and Pancreas 9-cis-Retinoic Acid Concentrations
Kane, M. A., Folias, A. E., Pingitore, A., Perri, M., Krois, C. R., Ryu, J. Y., Cione, E., & Napoli, J. L. (2011) · Molecular and Cellular Biology · doi:10.1128/mcb.05516-11 · Cited by 48 · see citing works
NIK links inflammation to hepatic steatosis by suppressing PPARα in alcoholic liver disease
Li, Y., Chen, M., Zhou, Y., Tang, C., Zhang, W., Zhong, Y., Chen, Y., Zhou, H. Y., & Sheng, L. (2020) · Theranostics · doi:10.7150/thno.40149 · Cited by 47 · see citing works
Exercise Intensity Modulation of Hepatic Lipid Metabolism
Lira, F. S., Carnevali, L. C., Zanchi, N. E., dos Santos, R. V. T., Lavoie, J.-M., & Seelaender, M. C. L. (2012) · Journal of Nutrition and Metabolism · doi:10.1155/2012/809576 · Cited by 47 · see citing works
Novel insight into glucagon receptor action: lessons from knockout and transgenic mouse models
Vuguin, P. M., & Charron, M. J. (2011) · Diabetes Obesity and Metabolism · doi:10.1111/j.1463-1326.2011.01447.x · Cited by 47 · see citing works
Self-citationGlucagon as a Critical Factor in the Pathology of Diabetes
Edgerton, D. S., & Cherrington, A. D. (2011) · Diabetes · doi:10.2337/db10-1594 · Cited by 47 · see citing works
Wang, H., Zhao, M., Sud, N., Christian, P., Shen, J., Song, Y., Pashaj, A., Zhang, K., Carr, T. P., & Su, Q. (2016) · Scientific Reports · doi:10.1038/srep32246 · Cited by 47 · see citing works
Möllmann, J., Kahles, F., Lebherz, C., Kappel, B. A., Baeck, C., Tacke, F., Werner, C., Federici, M., Marx, N., & Lehrke, M. (2016) · Diabetes Obesity and Metabolism · doi:10.1111/dom.12839 · Cited by 48 · see citing works
Sheng, L., Cho, K. W., Zhou, Y., Shen, H., & Rui, L. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.256677 · Cited by 45 · see citing works
- Authors
- Longuet, C., Sinclair, E. M., Maida, A., Baggio, L. L., Maziarz, M., Charron, M. J., & Drucker, D. J.
- Affiliations
- Mount Sinai Hospital (CA)
- Albert Einstein College of Medicine (US)
- Corresponding author
- Drucker, Daniel J.
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2008-11
- Volume
- 8
- Issue
- 5
- Pages
- 359-371
- ISSN
- 1550-4131 (ISSN-L)
- PMC
- PMC2593715
- OpenAlex
- W2085330452
- Cited by
- 272
- References
- 47
- Citations by year
- 2026: 14 · 2025: 16 · 2024: 23 · 2023: 17 · 2022: 17 · 2021: 16 · 2020: 17 · 2019: 14 · 2018: 10 · 2017: 20 · 2016: 10 · 2015: 19 · 2014: 18 · 2013: 12 · 2012: 20
- FWCI
- 3.98
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Funders
- Canadian Institutes of Health Research (10903)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK047425, R01DK47425)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Keywords
- glucagon receptor, fasting, hepatic lipid metabolism, fatty acid oxidation, hepatic triglyceride secretion, triglyceride synthesis, PPARα, glucagon, hepatic glucose production
- MeSH terms
- Adaptation, Biological, Animals, Cells, Cultured, Fasting, Fatty Acids, Female, Glucagon, Male, Oxidation-Reduction, RNA, Messenger, Triglycerides, Receptors, Glucagon, Mice, Knockout, Hepatocytes, PPAR alpha, p38 Mitogen-Activated Protein Kinases, Lipid Metabolism, Mice, AMP-Activated Protein Kinases
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