Physiologic action of glucagon on liver glucose metabolism
Open accessAbstract
Glucagon is a primary regulator of hepatic glucose production (HGP) in vivo during fasting, exercise and hypoglycaemia. Glucagon also plays a role in limiting hepatic glucose uptake and producing the hyperglycaemic phenotype associated with insulin deficiency and insulin resistance. In response to a physiological rise in glucagon, HGP is rapidly stimulated. This increase in HGP is entirely attributable to an enhancement of glycogenolysis, with little to no acute effect on gluconeogenesis. This dramatic rise in glycogenolysis in response to hyperglucagonemia wanes with time. A component of this waning effect is known to be independent of hyperglycemia, though the molecular basis for this tachyphylaxis is not fully understood. In the overnight fasted state, the presence of basal glucagon secretion is essential in countering the suppressive effects of basal insulin, resulting in the maintenance of appropriate levels of glycogenolysis, fasting HGP and blood glucose. The enhancement of glycogenolysis in response to elevated glucagon is critical in the life-preserving counterregulatory response to hypoglycaemia, as well as a key factor in providing adequate circulating glucose for working muscle during exercise. Finally, glucagon has a key role in promoting the catabolic consequences associated with states of deficient insulin action, which supports the therapeutic potential in developing glucagon receptor antagonists or inhibitors of glucagon secretion.
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?
Glucagon stimulates hepatic glycogenolysis and ketogenesis, and decreased insulin suppresses hepatocyte malonyl-CoA synthesis and lipogenesis, with concomitant activation of fatty acid oxidation.
“Glucagon stimulates hepatic glycogenolysis and ketogenesis, and the decrease in insulin suppresses hepatocyte malonyl-coenzyme A (CoA) synthesis and lipogenesis, with concomitant activation of FAO (21, 22).”
From Metabolic Flexibility as an Adaptation to Energy Resources and Requirements in Health and Disease (2018) · cites this paper as [21]
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
Intensive insulin therapy in critically ill patients.
Van den Berghe, G., Wouters, P., Weekers, F., Verwaest, C., Bruyninckx, F., Schetz, M., Vlasselaers, D., Ferdinande, P., Lauwers, P., & Bouillon, R. (2001) · New England Journal of Medicine · doi:10.1056/nejmoa011300 · Cited by 9,977 · see citing works
Abnormal Alpha-Cell Function in Diabetes: Response to Carbohydrate and Protein Ingestion
Müller, W. A., Faloona, G. R., Aguilar-Parada, E., & Unger, R. H. (1970) · New England Journal of Medicine · doi:10.1056/nejm197007162830301 · Cited by 626 · see citing works
Banting Lecture 1997. Control of glucose uptake and release by the liver in vivo.
Cherrington, A. D. (1999) · Diabetes · doi:10.2337/diabetes.48.5.1198 · Cited by 500 · see citing works
Shah, P., Vella, A., Basu, A., Basu, R., Schwenk, W. F., & Rizza, R. A. (2000) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.85.11.6993 · Cited by 368 · see citing works
Glucose counterregulation, hypoglycemia, and intensive insulin therapy in diabetes mellitus
Epstein, F. H., Cryer, P. E., & Gerich, J. E. (1985) · New England Journal of Medicine · doi:10.1056/nejm198507253130405 · Cited by 273 · see citing works
Cherrington, A. D., Chiasson, J. L., Liljenquist, J. E., Jennings, A. S., Keller, U., & Lacy, W. W. (1976) · Journal of Clinical Investigation · doi:10.1172/jci108596 · Cited by 249 · see citing works
Effect of glucagon on glucose production during insulin deficiency in the dog.
Cherrington, A. D., LACY, W. W., & Chiasson, J. L. (1978) · Journal of Clinical Investigation · doi:10.1172/jci109174 · Cited by 213 · see citing works
Role of Brain in Counterregulation of Insulin-Induced Hypoglycemia in Dogs
Biggers, D. W., Myers, S. R., Neal, D. W., Stinson, R. L., Cooper, N. B., Jaspan, J. B., Williams, P. E., Cherrington, A. D., & Frizzell, R. T. (1989) · Diabetes · doi:10.2337/diab.38.1.7 · Cited by 192 · see citing works
LILJENQUIST, J. E., Mueller, G., Cherrington, A. D., Keller, U. B., Chiasson, J. L., Perry, J., LACY, W. W., & Rabinowitz, D. L. (1977) · Journal of Clinical Investigation · doi:10.1172/jci108649 · Cited by 164 · see citing works
Glucagon is a primary controller of hepatic glycogenolysis and gluconeogenesis during muscular work
Wasserman, D. H., Spalding, J. A., Lacy, D. B., Colburn, C. A., Goldstein, R. E., & Cherrington, A. D. (1989) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1989.257.1.e108 · Cited by 155 · see citing works
Insulin Reciprocally Regulates Glucagon Secretion in Humans
Cooperberg, B. A., & Cryer, P. E. (2010) · Diabetes · doi:10.2337/db10-0728 · Cited by 145 · 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
Characterization of the Glucagon Response to Hypoglycemia in Man
Gerich, J. E., Schneider, V. B., Dippe, S. E., Langlois, M., Noacco, C., Karam, J. H., & Forsham, P. H. (1974) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-38-1-77 · Cited by 120 · 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 105 · see citing works
DEFECTIVE GLUCOSE HOMEOSTASIS DURING INFECTION
McGuinness, O. P. (2005) · Annual Review of Nutrition · doi:10.1146/annurev.nutr.24.012003.132159 · Cited by 100 · see citing works
Comparison of the direct and indirect effects of epinephrine on hepatic glucose production.
Chu, C. A., Sindelar, D. K., Neal, D. W., Allen, E. J., Donahue, E. P., & Cherrington, A. D. (1997) · Journal of Clinical Investigation · doi:10.1172/jci119232 · Cited by 81 · see citing works
Frizzell, R. T., Hendrick, G. K., Biggers, D. W., Lacy, D. B., Donahue, D. P., Green, D. R., Carr, R. K., Williams, P. E., Stevenson, R. W., & Cherrington, A. D. (1988) · Diabetes · doi:10.2337/diab.37.6.749 · Cited by 81 · see citing works
Cloning and sequence analysis of the murine glucagon receptor-encoding gene
Burcelin, R., Li, J., & Charron, M. J. (1995) · Gene · doi:10.1016/0378-1119(95)00472-i · Cited by 78 · see citing works
Importance of hypoglycemia-induced glucose production during isolated glucagon deficiency.
Cherrington, A. D., LILJENQUIST, J. E., Shulman, G. I., Williams, P. E., & LACY, W. W. (1979) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1979.236.3.e263 · Cited by 67 · see citing works
Proteolysis in homogenates of perfused rat liver: Responses to insulin, glucagon and amino acids
Mortimore, G. E., Neely, A. N., Cox, J. R., & Guinivan, R. A. (1973) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(73)90892-9 · Cited by 63 · see citing works
Holste, L. C., Connolly, C. C., Moore, M. C., Neal, D. W., & Cherrington, A. D. (1997) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1997.273.3.e488 · Cited by 48 · see citing works
Myers, S. R., Diamond, M. P., Adkins-Marshall, B. A., Williams, P. E., Stinsen, R., & Cherrington, A. D. (1991) · Metabolism · doi:10.1016/0026-0495(91)90194-2 · Cited by 47 · see citing works
Shulman, G. I., Williams, P. E., LILJENQUIST, J. E., LACY, W. W., Keller, U. B., & Cherrington, A. D. (1980) · Metabolism · doi:10.1016/0026-0495(80)90004-9 · Cited by 47 · see citing works
Glucagon 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
The Roles of Insulin and Glucagon in the Regulation of Gluconeogenesis in the Postabsorptive Dog
Jennings, A. S., Cherrington, A. D., LILJENQUIST, J. E., Keller, U. B., LACY, W. W., & Chiasson, J. L. (1977) · Diabetes · doi:10.2337/diab.26.9.847 · Cited by 47 · see citing works
Insulin-induced hypoglycemia increases hepatic sensitivity to glucagon in dogs
Rivera, N., Ramnanan, C. J., An, Z., Farmer, T. E., Smith, M. S., Farmer, B., Irimia, J. M., Snead, W. L., Lautz, M., Roach, P. J., et al. (2010) · Journal of Clinical Investigation · doi:10.1172/jci40919 · Cited by 46 · see citing works
Effects of insulin on glucagon-stimulated glucose production in the conscious dog
Steiner, K., Williams, P. E., LACY, W. W., & Cherrington, A. D. (1990) · Metabolism · doi:10.1016/0026-0495(90)90192-f · Cited by 46 · see citing works
Dobbins, R. L., Davis, S. N., Neal, D. W., Cobelli, C., & Cherrington, A. D. (1994) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1994.266.3.e467 · Cited by 37 · see citing works
Self-citationStevenson, R. W., Williams, P. E., & Cherrington, A. D. (1987) · Diabetologia · doi:10.1007/bf00275744 · Cited by 34 · see citing works
Role of glucagon in countering hypoglycemia induced by insulin infusion in dogs
Dobbins, R. L., Connolly, C. C., Neal, D. W., Palladino, L. J., Parlow, A. F., & Cherrington, A. D. (1991) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1991.261.6.e773 · Cited by 29 · see citing works
α- and β-Cell Responses to Small Changes in Plasma Glucose in the Conscious Dog
Flattem, N. L., Igawa, K., Shiota, M., Emshwiller, M., Neal, D. W., & Cherrington, A. D. (2001) · Diabetes · doi:10.2337/diabetes.50.2.367 · Cited by 29 · see citing works
Wada, M., Connolly, C. C., Tarumi, C., Neal, D. W., & Cherrington, A. D. (1995) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1995.268.2.e194 · Cited by 23 · see citing works
Frizzell, R. T., Hendrick, G. K., Biggers, D. W., et al. (1988) · Diabetes · doi:10.2337/diabetes.37.6.749 · Cited by 21 · see citing works
Hepatic and muscle glucose metabolism during total parenteral nutrition: impact of infection
McGuinness, O. P., Donmoyer, C. M., Ejiofor, J., McElligott, S. E., & Lacy, D. B. (1998) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1998.275.5.e763 · Cited by 18 · see citing works
Glucagon chronically impairs hepatic and muscle glucose disposal
Chen, S., Zhang, Y., Santomango, T. S., Williams, P. E., Lacy, D. B., & McGuinness, O. P. (2006) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00063.2006 · Cited by 17 · see citing works
Effect of acute glucagon removal on metabolic response to infection in conscious dog
McGuinness, O. P., Lacy, D. B., & Anderson, J. (1995) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1995.268.1.e92 · Cited by 13 · see citing works
Time course of the hepatic adaptation to TPN: interaction with glycogen depletion
Chen, S., Torres-Sanchez, C. J., Hosein, N., Zhang, Y., Lacy, D. B., & McGuinness, O. P. (2004) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00192.2004 · Cited by 9 · see citing works
Impact of infection on glucose-dependent liver glucose uptake during TPN: interaction with insulin
Chen, S., Donmoyer, C. M., Pearson, D., Poole, A., Zhang, Y., Lacy, D. B., & McGuinness, O. P. (2004) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00286.2003 · Cited by 8 · see citing works
Chen, S., Santomango, T. S., Williams, P. E., Lacy, D. B., & McGuinness, O. P. (2009) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.90821.2008 · Cited by 5 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Metabolic Flexibility as an Adaptation to Energy Resources and Requirements in Health and Disease
Smith, R. L., Soeters, M. R., Wüst, R. C. I., & Houtkooper, R. H. (2018) · Endocrine Reviews · doi:10.1210/er.2017-00211 · Cited by 787 · see citing works
Physiology 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
Unraveling the Regulation of Hepatic Metabolism by Insulin
Titchenell, P. M., Lazar, M. A., & Birnbaum, M. J. (2017) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2017.03.003 · Cited by 434 · see citing works
Resolving the paradox of hepatic insulin resistance
Santoleri, D., & Titchenell, P. M. (2019) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2018.10.016 · Cited by 336 · see citing works
Benner, C., van der Meulen, T., Cacéres, E., Tigyi, K., Donaldson, C. J., & Huising, M. O. (2014) · BMC Genomics · doi:10.1186/1471-2164-15-620 · Cited by 302 · see citing works
Urocortin3 mediates somatostatin-dependent negative feedback control of insulin secretion
van der Meulen, T., Donaldson, C. J., Cáceres, E., Hunter, A. E., Cowing-Zitron, C., Pound, L. D., Adams, M. W., Zembrzycki, A., Grove, K. L., & Huising, M. O. (2015) · Nature Medicine · doi:10.1038/nm.3872 · Cited by 256 · see citing works
Minireview: Glucagon in the Pathogenesis of Hypoglycemia and Hyperglycemia in Diabetes
Cryer, P. E. (2012) · Endocrinology · doi:10.1210/en.2011-1499 · Cited by 242 · 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
Brain insulin signalling in metabolic homeostasis and disease
Scherer, T., Sakamoto, K., & Buettner, C. (2021) · Nature Reviews Endocrinology · doi:10.1038/s41574-021-00498-x · Cited by 205 · 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
Hypothalamic-autonomic control of energy homeostasis
Seoane‐Collazo, P., Fernø, J., González, F., Diéguez, C., Leis, R., Nogueiras, R., & López, M. (2015) · Endocrine · doi:10.1007/s12020-015-0658-y · Cited by 188 · see citing works
Human hepatic 3D spheroids as a model for steatosis and insulin resistance
Kozyra, M., Johansson, I., Nordling, Å., Ullah, S., Lauschke, V. M., & Ingelman‐Sundberg, M. (2018) · Scientific Reports · doi:10.1038/s41598-018-32722-6 · Cited by 173 · 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
Adaptive reciprocity of lipid and glucose metabolism in human short-term starvation
Soeters, M. R., Soeters, P. B., Schooneman, M. G., Houten, S. M., & Romijn, J. A. (2012) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00397.2012 · Cited by 177 · see citing works
Glucagon Regulation of Energy Expenditure
Kleinert, M., Sachs, S., Habegger, K. M., Hofmann, S. M., & Müller, T. D. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20215407 · Cited by 147 · see citing works
Pathogenesis of Type 2 Diabetes Mellitus
Al-Saraj, F. (2015) · InTech eBooks · doi:10.5772/59183 · Cited by 139 · see citing works
The Biology of Glucagon and the Consequences of Hyperglucagonemia
Albrechtsen, N. J. W., Kuhre, R. E., Pedersen, J., Knop, F. K., & Holst, J. J. (2016) · Biomarkers in Medicine · doi:10.2217/bmm-2016-0090 · Cited by 124 · see citing works
Circulating follistatin is liver-derived and regulated by the glucagon-to-insulin ratio
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., et al. (2016) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2015-3668 · Cited by 125 · see citing works
Role of transcription factors in the transdifferentiation of pancreatic islet cells
van der Meulen, T., & Huising, M. O. (2015) · Journal of Molecular Endocrinology · doi:10.1530/jme-14-0290 · Cited by 113 · see citing works
Central mechanisms of glucose sensing and counterregulation in defense of hypoglycemia
Stanley, S., Moheet, A., & Seaquist, E. R. (2019) · Endocrine Reviews · doi:10.1210/er.2018-00226 · Cited by 112 · see citing works
Pathway to Artificial Pancreas Systems Revisited: Moving Downstream
Kowalski, A. J. (2015) · Diabetes Care · doi:10.2337/dc15-0364 · Cited by 113 · see citing works
New insights into the architecture of the islet of Langerhans: a focused cross-species assessment
Drigo, R. A. E., Ali, Y., Diez, J. A., Srinivasan, D. K., Berggren, P., & Boehm, B. (2015) · Diabetologia · doi:10.1007/s00125-015-3699-0 · Cited by 103 · 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
Berger, J. H., Charron, M. J., & Silver, D. L. (2012) · PLoS ONE · doi:10.1371/journal.pone.0050629 · Cited by 105 · see citing works
Hepatic Steatosis in Type 1 Diabetes
Regnell, S. E., & Lernmark, Å. (2011) · The Review of Diabetic Studies · doi:10.1900/rds.2011.8.454 · Cited by 105 · see citing works
Increased Adiposity, Dysregulated Glucose Metabolism and Systemic Inflammation in Galectin-3 KO Mice
Pang, J., Rhodes, D., Pini, M., Akasheh, R. T., Castellanos, K. J., Cabay, R. J., Cooper, D., Perretti, M., & Fantuzzi, G. (2013) · PLoS ONE · doi:10.1371/journal.pone.0057915 · Cited by 103 · see citing works
Hormonal and Metabolite Regulation of Hepatic Glucokinase
Agius, L. (2016) · Annual Review of Nutrition · doi:10.1146/annurev-nutr-071715-051145 · Cited by 101 · see citing works
Spatial metabolomics and its application in the liver
Santos, A. A., Delgado, T. C., Marques, V., Ramírez-Moncayo, C., Alonso, C., Vidal‐Puig, A., Hall, Z., Martínez‐Chantar, M. L., & Rodrigues, C. M. P. (2023) · Hepatology · doi:10.1097/hep.0000000000000341 · Cited by 100 · see citing works
Beheshti, A., Chakravarty, K., Fogle, H., Fazelinia, H., Silveira, W. A. D., Boyko, V., Polo, S.-H. L., Saravia-Butler, A. M., Hardiman, G., Taylor, D., et al. (2019) · Scientific Reports · doi:10.1038/s41598-019-55869-2 · Cited by 90 · see citing works
Yabe, D., Nishikino, R., Kaneko, M., Iwasaki, M., & Seino, Y. (2015) · Expert Opinion on Drug Safety · doi:10.1517/14740338.2015.1034105 · Cited by 98 · see citing works
Kokil, G. R., Veedu, R. N., Ramm, G. A., Prins, J. B., & Parekh, H. S. (2015) · Chemical Reviews · doi:10.1021/cr5002832 · Cited by 98 · see citing works
Hepatic glucose sensing and integrative pathways in the liver
Oosterveer, M. H., & Schoonjans, K. (2013) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-013-1505-z · Cited by 96 · see citing works
Alteration of the Glucagon Axis in GPR120 (FFAR4) Knockout Mice
Suckow, A. T., Polidori, D., Yan, W., Chon, S., Jing, Y., Leonard, J. N., & Briscoe, C. P. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.568683 · Cited by 94 · see citing works
MicroRNAs as pharmacological targets in diabetes
Mao, Y., Mohan, R., Zhang, S., & Tang, X. (2013) · Pharmacological Research · doi:10.1016/j.phrs.2013.06.005 · Cited by 85 · see citing works
Starvation Ketosis and the Kidney
Palmer, B. F., & Clegg, D. J. (2021) · American Journal of Nephrology · doi:10.1159/000517305 · Cited by 87 · see citing works
de Sousa, M. V., Fukui, R. T., Krustrup, P., Pereira, R. M. R., Silva, P. R. S., Rodrigues, A. C., Andrade, J. L., Hernandez, A. J., & da Silva, M. E. R. (2014) · Scandinavian Journal of Medicine and Science in Sports · doi:10.1111/sms.12258 · Cited by 81 · see citing works
Miao, L., Zhang, H., Cheong, M. S., Zhong, R., Garcia‐Oliveira, P., Prieto, M. A., Cheng, K., Wang, M., Cao, H., Nie, S., et al. (2023) · Food Science and Human Wellness · doi:10.1016/j.fshw.2023.03.021 · Cited by 76 · see citing works
Regulation of islet glucagon secretion: Beyond calcium
Hughes, J. W., Ustione, A., Lavagnino, Z., & Piston, D. W. (2018) · Diabetes Obesity and Metabolism · doi:10.1111/dom.13381 · Cited by 75 · see citing works
Brun, P., Grijalva, A., Rausch, R. N., Watson, E., Yuen, J. J., Das, B. C., Shudo, K., Kagechika, H., Leibel, R. L., & Blaner, W. S. (2014) · The FASEB Journal · doi:10.1096/fj.14-256743 · Cited by 70 · see citing works
Lipid droplets, bioenergetic fluxes, and metabolic flexibility
Bosch, M., Parton, R. G., & Pol, A. (2020) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2020.02.010 · Cited by 67 · see citing works
Neuroinflammatory and autonomic mechanisms in diabetes and hypertension
Han, C., Rice, M. W., & Cai, D. (2016) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00012.2016 · Cited by 63 · see citing works
Li, X., Shan, J., Chang, W., Kim, I., Bao, J., Lee, H., Zhang, X., Samuel, V. T., Shulman, G. I., Liu, D., et al. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1205015109 · 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
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
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
Skeletal muscle salt inducible kinase 1 promotes insulin resistance in obesity
Nixon, M., Stewart-Fitzgibbon, R., Fu, J., Akhmedov, D., Rajendran, K., Mendoza‐Rodriguez, M. G., Rivera-Molina, Y. A., Gibson, M., Berglund, E. D., Justice, N. J., et al. (2015) · Molecular Metabolism · doi:10.1016/j.molmet.2015.10.004 · Cited by 57 · see citing works
Metabolic roles of G protein‐coupled receptor signaling in obesity and type 2 diabetes
Barella, L. F., Jain, S., Kimura, T., & Pydi, S. P. (2021) · FEBS Journal · doi:10.1111/febs.15800 · Cited by 56 · see citing works
Glycemic Responses of Milk and Plant-Based Drinks: Food Matrix Effects
Shkembi, B., & Huppertz, T. (2023) · Foods · doi:10.3390/foods12030453 · Cited by 60 · see citing works
Endoplasmic reticulum-mitochondria calcium signaling in hepatic metabolic diseases
Rieusset, J. (2017) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2017.01.001 · Cited by 55 · see citing works
Drougard, A., Duparc, T., Brénachot, X., Carneiro, L., Gouazé, A., Fournel, A., Geurts, L., Cadoudal, T., Prats, A., Pénicaud, L., et al. (2013) · Antioxidants and Redox Signaling · doi:10.1089/ars.2013.5182 · Cited by 54 · see citing works
Merabet, N., Lucassen, P. J., Crielaard, L., Stronks, K., Quax, R., Sloot, P. M. A., la Fleur, S. E., & Nicolaou, M. (2021) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2021.100972 · Cited by 62 · see citing works
Youssef, J. E., Castle, J. R., Bakhtiani, P. A., Haidar, A., Branigan, D. L., Breen, M. E., & Ward, W. K. (2014) · Diabetes Care · doi:10.2337/dc14-0803 · Cited by 52 · see citing works
Treating type 1 diabetes: from strategies for insulin delivery to dual hormonal control.
McCall, A. L., & Farhy, L. S. (2013) · PubMed · Cited by 52 · see citing works
Čater, M., & Bombek, L. K. (2022) · Antioxidants · doi:10.3390/antiox11081473 · Cited by 51 · 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
Amigo, I., Traba, J., González‐Barroso, M. M., Rueda, C. B., Fernández, M., Rial, E., Sánchez, A., Satrústegui, J., & del Arco, A. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.409144 · Cited by 51 · see citing works
CRTC2 Is a Coactivator of GR and Couples GR and CREB in the Regulation of Hepatic Gluconeogenesis
Hill, M. J., Suzuki, S., Segars, J. H., & Kino, T. (2015) · Molecular Endocrinology · doi:10.1210/me.2015-1237 · Cited by 51 · see citing works
Pancreatic α-cell hyperplasia and hyperglucagonemia due to a glucagon receptor splice mutation
Larger, É., Albrechtsen, N. J. W., Hansen, L., Gelling, R. W., Capeau, J., Deacon, C. F., Madsen, O. D., Yakushiji, F., MEYTS, P. D., Holst, J. J., et al. (2016) · Endocrinology Diabetes and Metabolism Case Reports · doi:10.1530/edm-16-0081 · Cited by 51 · see citing works
Hypothalamic Dysfunction in Obesity and Metabolic Disorders
Carmo‐Silva, S., & Cavadas, C. (2017) · Advances in neurobiology · doi:10.1007/978-3-319-63260-5_4 · Cited by 51 · see citing works
Insulin therapy, weight gain and prognosis
Hodish, I. (2018) · Diabetes Obesity and Metabolism · doi:10.1111/dom.13367 · Cited by 48 · see citing works
Effect of acrylamide on glucose homeostasis in female rats and its mechanisms
Yue, Z., Chen, Y., Song, Y., Zhang, J., Yang, X., Wang, J., Li, L., & Sun, Z. (2019) · Food and Chemical Toxicology · doi:10.1016/j.fct.2019.110894 · Cited by 48 · see citing works
Potential role of non‐insulin adjunct therapy in Type 1 diabetes
George, P., & McCrimmon, R. J. (2012) · Diabetic Medicine · doi:10.1111/j.1464-5491.2012.03744.x · Cited by 49 · 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
Hedin, K. A., Zhang, H., Kruse, V., Rees, V. E., Bäckhed, F., Greiner, T. U., Vazquez-Uribe, R., & Sommer, M. O. A. (2023) · ACS Synthetic Biology · doi:10.1021/acssynbio.3c00455 · Cited by 45 · see citing works
Glucagon, from past to present: a century of intensive research and controversies
Scheen, A. J., & Lefèbvre, P. J. (2023) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(22)00349-7 · Cited by 44 · see citing works
Kimura, T., Pydi, S. P., Pham, J., & Tanaka, N. (2020) · Biomolecules · doi:10.3390/biom10101445 · Cited by 44 · see citing works
Metabolic Messengers: glucagon
MacDonald, P. E., & Rorsman, P. (2023) · Nature Metabolism · doi:10.1038/s42255-022-00725-3 · Cited by 44 · see citing works
Therapeutic approaches to non-alcoholic fatty liver disease: past achievements and future challenges
Xiao, J., Guo, R., Fung, M., Liong, E. C., & Tipoe, G. L. (2013) · Hepatobiliary & pancreatic diseases international · doi:10.1016/s1499-3872(13)60021-1 · Cited by 43 · see citing works
Glucagon’s effect on liver protein metabolism in vivo
Kraft, G., Coate, K. C., Winnick, J. J., Dardevet, D. P., Donahue, E. P., Cherrington, A. D., Williams, P. E., & Moore, M. C. (2017) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00045.2017 · Cited by 40 · see citing works
Schwartsburd, P. M. (2019) · Frontiers in Oncology · doi:10.3389/fonc.2019.00218 · Cited by 42 · see citing works
Aw, D. K. L., Sinha, R. A., Xie, S. Y., & Yen, P. M. (2014) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2014.04.031 · Cited by 41 · see citing works
Gs-DREADD Knock-In Mice for Tissue-Specific, Temporal Stimulation of Cyclic AMP Signaling
Akhmedov, D., Mendoza‐Rodriguez, M. G., Rajendran, K., Rossi, M., Wess, J., & Berdeaux, R. (2017) · Molecular and Cellular Biology · doi:10.1128/mcb.00584-16 · Cited by 40 · see citing works
The Vicious Circle of Hepatic Glucagon Resistance in Non-Alcoholic Fatty Liver Disease
Galsgaard, K. D. (2020) · Journal of Clinical Medicine · doi:10.3390/jcm9124049 · Cited by 39 · see citing works
Khare, P., Mangal, P., Baboota, R. K., Jagtap, S., Kumar, V., Singh, D. P., Boparai, R. K., Sharma, S. S., Khardori, R. K., Bhadada, S. K., et al. (2018) · Frontiers in Pharmacology · doi:10.3389/fphar.2018.01244 · Cited by 38 · see citing works
Regulation of hepatic gluconeogenesis by nuclear factor Y transcription factor in mice
Zhang, Y., Guan, Q., Liu, Y., Zhang, Y., Chen, Y., Chen, J., Liu, Y., & Su, Z. (2018) · Journal of Biological Chemistry · doi:10.1074/jbc.ra117.000508 · Cited by 37 · see citing works
Impairment of bisphenol F on the glucose metabolism of zebrafish larvae
Zhao, F., Wang, H., Wei, P., Jiang, G., Wang, W., Zhang, X., & Ru, S. (2018) · Ecotoxicology and Environmental Safety · doi:10.1016/j.ecoenv.2018.09.017 · Cited by 36 · see citing works
Zaborska, K. E., Dadi, P. K., Dickerson, M. T., Nakhe, A. Y., Thorson, A. S., Schaub, C. M., Graff, S. M., Stanley, J. E., Kondapavuluru, R. S., Denton, J. S., et al. (2020) · Molecular Metabolism · doi:10.1016/j.molmet.2020.101056 · Cited by 32 · see citing works
Montefusco, F., & Pedersen, M. G. (2015) · The Journal of Physiology · doi:10.1113/jp270777 · Cited by 35 · see citing works
Verlande, A., Chun, S. K., Goodson, M. O., Fortin, B. M., Bae, H., Jang, C., & Masri, S. (2021) · Science Advances · doi:10.1126/sciadv.abf3885 · Cited by 34 · see citing works
Dapagliflozin suppresses glucagon signaling in rodent models of diabetes
Wang, M.-Y., Yu, X., Lee, Y., McCorkle, S. K., Chen, S., Li, J., Wang, Z. V., Davidson, J. A., Scherer, P. E., Holland, W. L., et al. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1705845114 · Cited by 33 · see citing works
Mechanisms of action of incretin receptor based dual- and tri-agonists in pancreatic islets
Folli, F. B., Finzi, G., Manfrini, R., Galli, A., Casiraghi, F., Centofanti, L., Berra, C., Fiorina, P., Davalli, A. M., Rosa, S. L., et al. (2023) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00236.2023 · Cited by 32 · see citing works
Effect of Pramlintide on Postprandial Glucose Fluxes in Type 1 Diabetes
Hinshaw, L., Schiavon, M., Dadlani, V., Mallad, A., Man, C. D., Bharucha, A. E., Basu, R., Geske, J. R., Carter, R. E., Cobelli, C., et al. (2016) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2015-3952 · Cited by 32 · see citing works
The Glycosphingolipid GM3 Modulates Conformational Dynamics of the Glucagon Receptor
Ansell, T. B., Song, W., & Sansom, M. S. P. (2020) · Biophysical Journal · doi:10.1016/j.bpj.2020.06.009 · Cited by 32 · see citing works
Tavares, C. D. J., Aigner, S., Sharabi, K., Sathe, S., Mutlu, B., Yeo, G. W.-M., & Puigserver, P. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2000643117 · Cited by 31 · see citing works
Naik, A., Adeyemi, S. B., Vyas, B., & Krishnamurthy, R. (2021) · Journal of Traditional and Complementary Medicine · doi:10.1016/j.jtcme.2021.08.007 · Cited by 36 · see citing works
Boido, A., Ceriani, V., & Pontiroli, A. E. (2014) · Acta Diabetologica · doi:10.1007/s00592-014-0665-0 · Cited by 32 · see citing works
Chowdhury, M. K. H., Turner, N. A., Bentley, N. L., Das, A., Wu, L. E., Richani, D., Bustamante, S., Gilchrist, R. B., Morris, M. J., Shepherd, P. R., et al. (2017) · Scientific Reports · doi:10.1038/srep40159 · Cited by 32 · see citing works
Zhang, J., Zheng, Y., Martens, L., & Pfeiffer, A. F. H. (2023) · Nutrients · doi:10.3390/nu15183913 · Cited by 31 · see citing works
Peripheral Adrenoceptors: The Impetus Behind Glucose Dysregulation and Insulin Resistance
Boyda, H. N., Procyshyn, R. M., Pang, C. C. Y., & Barr, A. M. (2012) · Journal of Neuroendocrinology · doi:10.1111/jne.12002 · Cited by 29 · see citing works
Lee, M., Kim, M., Park, J. S., Lee, S., You, J. H., Ahn, C. W., Kim, K. R., & Kang, S. (2017) · The Korean Journal of Internal Medicine · doi:10.3904/kjim.2016.233 · Cited by 28 · see citing works
Hyperglycemia-induced changes in miRNA expression patterns in epicardial adipose tissue of piglets
Oclon, E. A., Latacz, A., Zubel–Łojek, J., & Pierzchała, K. (2016) · Journal of Endocrinology · doi:10.1530/joe-15-0495 · Cited by 29 · see citing works
Effects of intermittent fasting on liver physiology and metabolism in mice
Ma, J., Cheng, Y., Su, Q., Ai, W., Gong, L., Wang, Y., Li, L., Ma, Z., Pan, Q., Qiao, Z., et al. (2021) · Experimental and Therapeutic Medicine · doi:10.3892/etm.2021.10382 · Cited by 29 · see citing works
Cullen, K. S., Al‐Oanzi, Z. H., O'Harte, F. P. M., Agius, L., & Arden, C. (2014) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2014.02.006 · Cited by 28 · see citing works
Hinshaw, L., Mallad, A., Man, C. D., Basu, R., Cobelli, C., Carter, R. E., Kudva, Y. C., & Basu, A. (2015) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00236.2015 · Cited by 28 · see citing works
Zenz, S., Mader, J. K., Regittnig, W., Brunner, M., Korsatko, S., Boulgaropoulos, B., Magnes, C., Raml, R., Narath, S. H., Eller, P., et al. (2018) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2017-01836 · Cited by 29 · see citing works
Matsuhisa, M., Takita, Y., Nasu, R., Nagai, Y., Ohwaki, K., & Nagashima, H. (2020) · Diabetes, Obesity and Metabolism · doi:10.1111/dom.14019 · Cited by 27 · see citing works
Small molecule glucagon receptor antagonists: an updated patent review (2015–2019)
Cheng, C. Y., Jabri, S. Y., Taoka, B. M., & Sinz, C. J. (2020) · Expert Opinion on Therapeutic Patents · doi:10.1080/13543776.2020.1769600 · Cited by 27 · see citing works
Ittner, A., Bertz, J., Chan, T. Y. B., van Eersel, J., Polly, P., & Ittner, L. M. (2014) · Diabetologia · doi:10.1007/s00125-014-3230-z · Cited by 27 · see citing works
- Authors
- Ramnanan, C. J., Edgerton, D. S., Kraft, G., & Cherrington, A. D.
- Affiliations
- Vanderbilt University (US)
- Corresponding author
- Cherrington, A. D.
- Venue
- Diabetes Obesity and Metabolism
- Publisher
- Wiley
- Published
- 2011-08-08
- Volume
- 13
- Issue
- s1
- Pages
- 118-125
- ISSN
- 1462-8902 (ISSN-L)
- 1463-1326
- PMC
- PMC5371022
- OpenAlex
- W2013438463
- Cited by
- 293
- References
- 38
- Citations by year
- 2026: 15 · 2025: 21 · 2024: 15 · 2023: 34 · 2022: 16 · 2021: 32 · 2020: 16 · 2019: 21 · 2018: 15 · 2017: 21 · 2016: 14 · 2015: 25 · 2014: 16 · 2013: 19 · 2012: 11
- FWCI
- 2.70
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Diabetes Obesity and Metabolism (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- American Diabetes Association
- Vanderbilt University
- National Institutes of Health
- School of Medicine, Vanderbilt University
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK018243, P30DK020593)
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Keywords
- glucagon, hepatic glucose production, glycogenolysis, gluconeogenesis, tachyphylaxis, fasting, hypoglycemia, counterregulatory response, physical activity, insulin resistance, insulin deficiency, hepatic glucose uptake, glucagon receptor antagonists, glucagon secretion
- MeSH terms
- Animals, Blood Glucose, Dogs, Fasting, Glucagon, Gluconeogenesis, Insulin, Liver, Physical Conditioning, Animal
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
