The metabolic actions of glucagon revisited

Habegger, Kirk M.; Heppner, Kristy M.; Geary, Nori; Bartness, Timothy J.; DiMarchi, Richard; Tschöp, Matthias H.

doi:10.1038/nrendo.2010.187

Cited by 406Regulation of Appetite and ObesityDiabetes Treatment and ManagementAdipokines, Inflammation, and Metabolic Diseases

The metabolic actions of glucagon revisited

Open access

Habegger, Kirk M., Heppner, Kristy M., Geary, Nori, Bartness, Timothy J., DiMarchi, Richard, Tschöp, Matthias H.·2010·Nature Reviews Endocrinology

DOI 10.1038/nrendo.2010.187PMC PMC3563428

Open this paper in CoChat — free account

Abstract

The initial identification of glucagon as a counter-regulatory hormone to insulin revealed this hormone to be of largely singular physiological and pharmacological purpose. Glucagon agonism, however, has also been shown to exert effects on lipid metabolism, energy balance, body adipose tissue mass and food intake. The ability of glucagon to stimulate energy expenditure, along with its hypolipidemic and satiating effects, in particular, make this hormone an attractive pharmaceutical agent for the treatment of dyslipidemia and obesity. Studies that describe novel preclinical applications of glucagon, alone and in concert with glucagon-like peptide 1 agonism, have revealed potential benefits of glucagon agonism in the treatment of the metabolic syndrome. Collectively, these observations challenge us to thoroughly investigate the physiology and therapeutic potential of insulin's long-known opponent.

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

Crossref · 10.1038/nrendo.2010.187

Cites

129 of 129 references verified0 citation errors · 0 not checkable

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?

Beyond weight loss, retatrutide's lipid effects may be partly driven by its triple agonism, particularly glucagon receptor activation, which enhances lipid oxidation and reduces hepatic lipid synthesis.
“Beyond WL, these effects may be partly driven by its triple agonism, particularly glucagon receptor activation, which enhances lipid oxidation and reduces hepatic lipid synthesis [56].”
From Triple Agonism Based Therapies for Obesity (2025) · cites this paper as [56]
The “Glucagon and lipid metabolism” section reports that glucagon stimulated fatty-acid oxidation and inhibited lipogenesis in rabbit hepatocytes; it also reports increased oxidation in primary human hepatocytes. This supports the proposed glucagon mechanism, but the paper discusses glucagon–GLP-1 dual agonism, not retatrutide or triple agonism, so it does not establish that this mechanism drives retatrutide’s lipid effects. (LLM, conf=0.88)
Experimental — accuracy not yet measured
Glucagon acts not only to increase glucose production but also to induce lipolysis, fatty acid oxidation, ketogenesis, increase thermogenesis and energy expenditure, bile acid synthesis, and induce satiation and reduce food intake.
“Therefore, glucagon acts not only to increase glucose production but also to induce lipolysis, fatty acid oxidation, ketogenesis, increase thermogenesis and energy expenditure, bile acid synthesis, and finally induce satiation and reduce food intake [22, 23].”
From Dual and Triple Incretin-Based Co-agonists: Novel Therapeutics for Obesity and Diabetes (2024) · cites this paper as [22]
The sections on lipid metabolism, energy expenditure, and food intake support the claimed effects on lipolysis, fatty acid oxidation, ketogenesis, thermogenesis, energy expenditure, and satiation. The bile acid metabolism section does not establish that glucagon induces bile acid synthesis: it reports reduced expression of a rate-limiting enzyme and says the direct effect on synthesis remains unknown, although the lipid metabolism section reports elevated conversion of cholesterol to bile acids in rats. Page numbers were not available in our copy. (LLM, conf=0.86)
Experimental — accuracy not yet measured
Further glucagon actions include improvement of whole body lipid metabolism and promotion of hepatic fatty acid oxidation, which may provide therapeutic actions for MASLD and/or MASH.
“Further glucagon actions include the improvement of the whole body lipid metabolism and the promotion of hepatic fatty acid oxidation which may provide therapeutic actions for MASLD and/or MASH [60].”
From What is the pipeline for future medications for obesity? (2025) · cites this paper as [60]
In ‘Glucagon and lipid metabolism,’ the paper reports that glucagon increases fatty acid oxidation in primary human hepatocytes. ‘Glucagon-based pharmacological therapy’ describes hypolipidemic effects and suggests a possible treatment for fatty liver, but that treatment evidence comes from cattle and requires verification in nonruminants. The paper does not establish therapeutic benefit for MASLD or MASH specifically. (LLM, conf=0.86)
Experimental — accuracy not yet measured
Glucagon is secreted from pancreatic α-cells and its main physiological site of action is the liver to increase hepatic glucose production.
“Glucagon is secreted from the pancreatic a-cells and the main physiological site of action is the liver to increase hepatic glucose production [60].”
From What is the pipeline for future medications for obesity? (2025) · cites this paper as [60]
Glucagon has additional metabolic effects including increasing satiety, reducing food intake, effects on lipid homeostasis and increasing energy expenditure.
“Beyond the role of glucagon in glucose homeostasis, there are additional metabolic effects; these include increasing satiety and reducing food intake, as well as effects on lipid homeostasis and the increase of energy expenditure [8,9].”
From Results from three phase 1 trials of NNC9204-1177, a glucagon/GLP-1 receptor co-agonist: Effects on weight loss and safety in adults with overweight or obesity (2023) · cites this paper as [8]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

International Union of Pharmacology: Approaches to the Nomenclature of Voltage-Gated Ion Channels
Catterall, W. A., Chandy, K. G., Clapham, D. E., Gutman, G. A., Hofmann, F., Harmar, A. J., Abernethy, D. R., & Spedding, M. (2003) · Pharmacological Reviews · doi:10.1124/pr.55.4.5 · Cited by 7,126 · see citing works
Identification and Importance of Brown Adipose Tissue in Adult Humans
Cypess, A. M., Lehman, S., Williams, G., Tal, I., Rodman, D., Goldfine, A. B., Kuo, F. C., Palmer, E. L., Tseng, Y.-H., Doria, A., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0810780 · Cited by 4,399 · see citing works
Biology of Incretins: GLP-1 and GIP
Baggio, L. L., & Drucker, D. J. (2007) · Gastroenterology · doi:10.1053/j.gastro.2007.03.054 · Cited by 3,639 · see citing works
Control of hepatic gluconeogenesis through the transcriptional coactivator PGC-1
Yoon, J. C., Puigserver, P., Chen, G., Donovan, J., Wu, Z., Rhee, J., Adelmant, G., Stafford, J., Kahn, C. R., Granner, D. K., et al. (2001) · Nature · doi:10.1038/35093050 · Cited by 1,821 · see citing works
CREB regulates hepatic gluconeogenesis through the coactivator PGC-1
Herzig, S., Long, F., Jhala, U. S., Hedrick, S., Quinn, R., Bauer, A., Rudolph, D., Schutz, G., Yoon, C., Puigserver, P., et al. (2001) · Nature · doi:10.1038/35093131 · Cited by 1,440 · 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 996 · see citing works
Cyclic AMP
Robinson, G. A., Butcher, R. W., & Sutherland, E. W. (1968) · Annual Review of Biochemistry · doi:10.1146/annurev.bi.37.070168.001053 · Cited by 958 · 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
Autonomic regulation of islet hormone secretion – Implications for health and disease
Bo, A.-R. (2000) · Diabetologia · doi:10.1007/s001250051322 · Cited by 843 · see citing works
The Glucagon-sensitive Adenyl Cyclase System in Plasma Membranes of Rat Liver
Rodbell, M., Birnbaumer, L., Pohl, S. L., & Krans, H. M. J. (1971) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)62390-7 · Cited by 813 · see citing works
The internal secretion of the pancreas
Banting, F., & BEST, C. H. (1922) · Journal of Laboratory and Clinical Medicine · doi:10.5555/uri:pii:s0022214322903841 · Cited by 785 · see citing works
A new glucagon and GLP-1 co-agonist eliminates obesity in rodents
Day, J. W., Ottaway, N., Patterson, J. T., Gelfanov, V., Smiley, D., Gidda, J., Findeisen, H., Bruemmer, D., Drucker, D. J., Chaudhary, N., et al. (2009) · Nature Chemical Biology · doi:10.1038/nchembio.209 · Cited by 641 · see citing works
Self-citation
α-Cells of the Endocrine Pancreas: 35 Years of Research but the Enigma Remains
Gromada, J., Franklin, I., & Wollheim, C. B. (2007) · Endocrine Reviews · doi:10.1210/er.2006-0007 · Cited by 574 · see citing works
Lower blood glucose, hyperglucagonemia, and pancreatic α cell hyperplasia in glucagon receptor knockout mice
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
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
Bile Acid Regulation of Gene Expression: Roles of Nuclear Hormone Receptors
Chiang, J. Y. L. (2002) · Endocrine Reviews · doi:10.1210/er.2000-0035 · Cited by 484 · see citing works
The Glucagon-sensitive Adenyl Cyclase System in Plasma Membranes of Rat Liver
Pohl, S. L., Krans, H. M. J., Kozyreff, V., Birnbaumer, L., & Rodbell, M. (1971) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)62032-0 · Cited by 463 · see citing works
A 1 percent risk.
Ln, W. (1968) · PubMed · Cited by 434 · see citing works
TCF-4 Mediates Cell Type-specific Regulation of Proglucagon Gene Expression by β-Catenin and Glycogen Synthase Kinase-3β
Yi, F., Brubaker, P. L., & Jin, T. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m411487200 · Cited by 413 · 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
Expression 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
The role of α-cell dysregulation in fasting and postprandial hyperglycemia in type 2 diabetes and therapeutic implications
Dunning, B. E., & Gerich, J. E. (2007) · Endocrine Reviews · doi:10.1210/er.2006-0026 · Cited by 369 · see citing works
Effect of Diet and Cold Exposure on Norepinephrine Turnover in Brown Adipose Tissue of the Rat
Young, J. B., Saville, E., Rothwell, N. J., Stock, M. J., & Landsberg, L. (1982) · Journal of Clinical Investigation · doi:10.1172/jci110541 · Cited by 356 · see citing works
Prevention of Human Diabetic Ketoacidosis by Somatostatin
Gerich, J. E., Lorenzi, M., Bier, D. M., Schneider, V. B., Tsalikian, E., Karam, J. H., & Forsham, P. H. (1975) · New England Journal of Medicine · doi:10.1056/nejm197505082921901 · Cited by 353 · see citing works
Mice lacking dipeptidyl peptidase IV are protected against obesity and insulin resistance
Conarello, S., Li, Z., Ronan, J., Roy, R. S., Zhu, L., Jiang, G., Liu, F., Woods, J. W., Zycband, E., Moller, D. E., et al. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0631828100 · Cited by 346 · see citing works
Dipeptidyl Peptidase IV Inhibitor Treatment Stimulates β-Cell Survival and Islet Neogenesis in Streptozotocin-Induced Diabetic Rats
Pospisilik, J. A., Martin, J., Doty, T., Ehses, J. A., Pamir, N., Lynn, F. C., Piteau, S., Demuth, H.-U., McIntosh, C. H. S., & Pederson, R. A. (2003) · Diabetes · doi:10.2337/diabetes.52.3.741 · Cited by 332 · see citing works
Leptin therapy in insulin-deficient type I diabetes
Wang, M.-Y., Chen, L., Clark, G. O., Lee, Y., Stevens, R. D., Ilkayeva, O. R., Wenner, B. R., Bain, J. R., Charron, M. J., Newgard, C. B., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0909422107 · Cited by 327 · see citing works
β-Cell Secretory Products Activate α-Cell ATP-Dependent Potassium Channels to Inhibit Glucagon Release
Franklin, I., Gromada, J., Gjinovci, A., Theander, S., & Wollheim, C. (2005) · Diabetes · doi:10.2337/diabetes.54.6.1808 · Cited by 291 · see citing works
The Glucagon Receptor Is Required for the Adaptive Metabolic Response to Fasting
Longuet, C., Sinclair, E. M., Maida, A., Baggio, L. L., Maziarz, M., Charron, M. J., & Drucker, D. J. (2008) · Cell Metabolism · doi:10.1016/j.cmet.2008.09.008 · Cited by 272 · see citing works
Alpha cell function in health and disease: influence of glucagon-like peptide-1
Dunning, B. E., Foley, J. E., & Åhrén, B. (2005) · Diabetologia · doi:10.1007/s00125-005-1878-0 · Cited by 268 · see citing works
Glucose or Insulin, but not Zinc Ions, Inhibit Glucagon Secretion From Mouse Pancreatic α-Cells
Ravier, M. A., & Rutter, G. A. (2005) · Diabetes · doi:10.2337/diabetes.54.6.1789 · Cited by 264 · see citing works
The Effects of Glucagon, Dibutyryl Cyclic Adenosine 3',5'-Monophosphate, and Concentration of Free Fatty Acid on Hepatic Lipid Metabolism
Heimberg, M., Weinstein, I., & Kohout, M. (1969) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)63637-3 · Cited by 254 · see citing works
Physiology and pathophysiology of glucagon
Unger, R. H., & Orci, L. (1976) · Physiological Reviews · doi:10.1152/physrev.1976.56.4.778 · Cited by 254 · see citing works
A KATP Channel-Dependent Pathway within α Cells Regulates Glucagon Release from Both Rodent and Human Islets of Langerhans
MacDonald, P. E., Marinis, Y. Z. D., Ramracheya, R. D., Salehi, A. A., Ma, X., Johnson, P., Cox, R., Eliasson, L., & Rorsman, P. (2007) · PLoS Biology · doi:10.1371/journal.pbio.0050143 · Cited by 243 · see citing works
Glucagon receptors on human islet cells contribute to glucose competence of insulin release
Huypens, P., Ling, Z., Pipeleers, D., & Schuit, F. (2000) · Diabetologia · doi:10.1007/s001250051484 · Cited by 226 · see citing works
Glucagon receptor knockout mice are resistant to diet-induced obesity and streptozotocin-mediated beta cell loss and hyperglycaemia
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
MafB
Artner, I., Lay, J. E. L., Hang, Y., Elghazi, L., Schisler, J. C., Henderson, E., Sosa‐Pineda, B., & Stein, R. W. (2006) · Diabetes · doi:10.2337/diabetes.55.02.06.db05-0946 · Cited by 209 · see citing works
Effect of beta-hydroxybutyrate on whole-body leucine kinetics and fractional mixed skeletal muscle protein synthesis in humans.
Nair, K. S., Welle, S. L., Halliday, D., & Campbell, R. G. (1988) · Journal of Clinical Investigation · doi:10.1172/jci113570 · Cited by 201 · see citing works
Sequential Serum-dependent Activation of CREB and NRF-1 Leads to Enhanced Mitochondrial Respiration through the Induction of Cytochrome c
Herzig, R. P., Scacco, S., & Scarpulla, R. C. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.17.13134 · Cited by 197 · see citing works
Adrenaline Stimulates Glucagon Secretion in Pancreatic A-Cells by Increasing the Ca2+ Current and the Number of Granules Close to the L-Type Ca2+ Channels
Gromada, J., Bokvist, K., Ding, W.-G., Barg, S., Buschard, K., Renström, E., & Rorsman, P. (1997) · The Journal of General Physiology · doi:10.1085/jgp.110.3.217 · Cited by 196 · see citing works
Hypothalamic influence on insulin and glucagon release in the rat.
de Jong, A., Strubbe, J. H., & Steffens, A. B. (1977) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1977.233.5.e380 · Cited by 183 · see citing works
Effect of Glucagon on Food Intake and Body Weight in Man
Schulman, J. L., Carleton, J. L., Whitney, G., & Whitehorn, J. C. (1957) · Journal of Applied Physiology · doi:10.1152/jappl.1957.11.3.419 · Cited by 174 · see citing works
The Mechanism of Satiety: Effect of Glucagon on Gastric Hunger Contractions in Man.
Stunkard, A. J., Itallie, T. B. V., & Reis, B. B. (1955) · Experimental Biology and Medicine · doi:10.3181/00379727-89-21776 · Cited by 160 · see citing works
Glucose Stimulates Glucagon Release in Single Rat α-Cells by Mechanisms that Mirror the Stimulus-Secretion Coupling in β-Cells
Olsen, H. L., Theander, S., Bokvist, K., Buschard, K., Wollheim, C. B., & Gromada, J. (2005) · Endocrinology · doi:10.1210/en.2005-0800 · Cited by 156 · see citing works
Cross Talk between the Insulin and Wnt Signaling Pathways: Evidence from Intestinal Endocrine L Cells
Yi, F., Sun, J., Lim, G. E., Fantus, I. G., Brubaker, P. L., & Jin, T. (2008) · Endocrinology · doi:10.1210/en.2007-1142 · Cited by 154 · see citing works
Relative quantitative analysis of glucagon receptor mRNA in rat tissues
Svoboda, M., Tastenoy, M., Vertongen, P., & Robberecht, P. (1994) · Molecular and Cellular Endocrinology · doi:10.1016/0303-7207(94)90162-7 · Cited by 152 · see citing works
Stimulation of Feeding in Rats by Intraperitoneal Injection of Antibodies to Glucagon
Langhans, W., Zeiger, U., Scharrer, E., & Geary, N. (1982) · Science · doi:10.1126/science.7134979 · Cited by 151 · see citing works
Self-citation
Ethnicity, type 2 diabetes & migrant Asian Indians.
Abate, N., & Chandalia, M. (2007) · PubMed · Cited by 150 · see citing works
Insulin regulation of the glucagon gene is mediated by an insulin-responsive DNA element.
Philippe, J. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.16.7224 · Cited by 144 · see citing works
Postprandial Suppression of Glucagon Secretion Depends on Intact Pulsatile Insulin Secretion
Meier, J. J., Kjems, L. L., Veldhuis, J. D., Lefèbvre, P., & Butler, P. C. (2006) · Diabetes · doi:10.2337/diabetes.55.04.06.db05-1449 · Cited by 144 · see citing works
AQUEOUS EXTRACTS OF PANCREAS
Murlin, J. R., Clough, H. D., Gibbs, C. B. F., & Stokes, A. M. (1923) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)85619-8 · Cited by 141 · see citing works
Hyperglucagonemia increases resting metabolic rate in man during insulin deficiency
NAIR, K. S. (1987) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-64-5-896 · Cited by 141 · see citing works
Differential sympathetic drive to adipose tissues after food deprivation, cold exposure or glucoprivation
Brito, N. A., Brito, M. N., & Bartness, T. J. (2008) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00068.2008 · Cited by 137 · see citing works
Self-citation
Individual, but not simultaneous, glucagon and cholecystokinin infusions inhibit feeding in men
Geary, N., Kissileff, H. R., Pi-Sunyer, X., & Hinton, V. J. (1992) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1992.262.6.r975 · Cited by 134 · see citing works
Self-citation
Selective hepatic vagotomy blocks pancreatic glucagon's satiety effect
GEARY, N., & SMITH, G. (1983) · Physiology & Behavior · doi:10.1016/0031-9384(83)90207-x · Cited by 134 · see citing works
Self-citation
Glucagon Represses Signaling through the Mammalian Target of Rapamycin in Rat Liver by Activating AMP-activated Protein Kinase
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
Glucagon acts in the liver to control spontaneous meal size in rats
Geary, N., Le Sauter, J., & Noh, U. (1993) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1993.264.1.r116 · Cited by 128 · see citing works
Self-citation
The role of cyclic AMP in the control of liver metabolism
Exton, J. H., & Park, C. R. (1968) · Advances in Enzyme Regulation · doi:10.1016/0065-2571(68)90024-1 · Cited by 126 · see citing works
Depression of Food Intake Induced in Healthy Subjects by Glucagon
Penick, S. B., Hinkle, L. E., & Paulsen, E. G. (1961) · New England Journal of Medicine · doi:10.1056/nejm196105042641801 · Cited by 125 · see citing works
The effect of propranalol on the calorigenic response in brown adipose tissue of new‐born rabbits to catecholamines, glucagon, corticotrophin and cold exposure
Heim, T. F., & Hull, D. (1966) · The Journal of Physiology · doi:10.1113/jphysiol.1966.sp008088 · Cited by 124 · see citing works
Decreased feeding in rats following hepatic-portal infusion of glucagon
Martin, J. R., & Novin, D. (1977) · Physiology & Behavior · doi:10.1016/0031-9384(77)90218-9 · Cited by 123 · see citing works
Hormonal regulation of cholesterol 7 alpha-hydroxylase mRNA levels and transcriptional activity in primary rat hepatocyte cultures.
Hylemon, P. B., Gurley, E. C., Stravitz, R. T., Litz, J., Pandak, W. M., Chiang, J. Y. L., & Vlahcevic, Z. R. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)41864-9 · Cited by 121 · see citing works
Glucagon Receptor Knockout Mice Display Increased Insulin Sensitivity and Impaired β-Cell Function
Sørensen, H., Winzell, M. S., Brand, C. L., Fosgerau, K., Gelling, R. W., Nishimura, E., & Åhrén, B. (2006) · Diabetes · doi:10.2337/db06-0307 · Cited by 120 · see citing works
Effects of ethanol on mitogen-activated protein kinase and stress-activated protein kinase cascades in normal and regenerating liver
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
Long-Term Inhibition of the Glucagon Receptor with a Monoclonal Antibody in Mice Causes Sustained Improvement in Glycemic Control, with Reversible α-Cell Hyperplasia and Hyperglucagonemia
Gu, W., Yan, H., Winters, K. A., Komorowski, R., Vonderfecht, S. L., Atangan, L. I., Sivits, G. N., Hill, D., Yang, J., Bi, V., et al. (2009) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.109.157685 · Cited by 105 · see citing works
Too Much Glucagon, Too Little Insulin
Brown, R. J., Sinaii, N., & Rother, K. I. (2008) · Diabetes Care · doi:10.2337/dc08-0575 · Cited by 104 · see citing works
Stimulation of Metabolism of Rat Brown Adipose Tissue by Addition of Lipolytic Hormones in Vitro
Joel, C. D. (1966) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)96838-9 · Cited by 102 · see citing works
Thermogenic Responses of Brown Adipocytes to Noradrenaline and Glucagon in Heat-acclimated and Cold-acclimated Rats
KUROSHIMA, A., & Yahata, T. (1979) · The Japanese Journal of Physiology · doi:10.2170/jjphysiol.29.683 · Cited by 100 · see citing works
Distribution of glucagon receptors on hormone-specific endocrine cells of rat pancreatic islets
Kieffer, T. J., Heller, R. S., Unson, C. G., Weir, G. C., & Habener, J. F. (1996) · Endocrinology · doi:10.1210/endo.137.11.8895386 · Cited by 89 · 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
Metabolic effects of glucagon in the Wistar rat
SALTER, J. M. (1960) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/8.5.535 · Cited by 85 · see citing works
Physiological Effect of Glucagon in Human Isolated Adipocytes
Perea, A., Clemente, F., Martinell, J., Villanueva-Peñacarrillo, M., & Valverde, I. (1995) · Hormone and Metabolic Research · doi:10.1055/s-2007-979981 · Cited by 84 · see citing works
Glucagon stimulation of brown adipose tissue growth and thermogenesis
Billington, C. J., Bartness, T. J., Briggs, J., Levine, A. S., & Morley, J. E. (1987) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1987.252.1.r160 · Cited by 78 · see citing works
Self-citation
Stimulation of rat hepatic low density lipoprotein receptors by glucagon. Evidence of a novel regulatory mechanism in vivo.
Rudling, M. J., & Angelin, B. (1993) · Journal of Clinical Investigation · doi:10.1172/jci116522 · Cited by 76 · see citing works
Evidence that the sensitivity of carnitine palmitoyltransferase I to inhibition by malonyl-CoA is an important site of regulation of hepatic fatty acid oxidation in the fetal and newborn rabbit. Perinatal development and effects of pancreatic hormones in cultured rabbit hepatocytes
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
The Effect of Glucagon on the Metabolic Rate of Rats
Davidson, I. W. F., Salter, J., & BEST, C. H. (1960) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/8.5.540 · Cited by 72 · see citing works
Glucagon in physiological concentrations stimulates brown fat thermogenesis in vivo
Billington, C. J., Briggs, J. E., Link, J. G., & Levine, A. S. (1991) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1991.261.2.r501 · Cited by 71 · see citing works
Glucagon and cAMP inhibit cholesterol 7α‐hydroxylase (CYP7a1) gene expression in human hepatocytes
Song, K., & Chiang, J. Y. L. (2005) · Hepatology · doi:10.1002/hep.20919 · Cited by 70 · see citing works
Loss of glucagon suppression of feeding after vagotomy in rats.
Martin, J. R., Novin, D., & Vanderweele, D. A. (1978) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1978.234.3.e314 · Cited by 69 · see citing works
Pancreatic β-cell overexpression of the glucagon receptor gene results in enhanced β-cell function and mass
Gelling, R. W., Vuguin, P. M., Du, X. Q., Cui, L., Rømer, J., Pederson, R. A., Leiser, M., Sørensen, H., Holst, J. J., Fledelius, C., et al. (2009) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00082.2009 · Cited by 67 · see citing works
Calorigenic action of glucagon
DAVIDSON, I. W. F., SALTER, J. M., & BEST, C. H. (1957) · Nature · doi:10.1038/1801124a0 · Cited by 66 · see citing works
Effect of Glucagon on the Metabolism of Lipids and on Urea Formation by the Perfused Rat Liver
Penhos, J. C., Wu, C. H., Daunas, J. A., Reitman, M. J., & Levune, R. (1966) · Diabetes · doi:10.2337/diab.15.10.740 · Cited by 66 · see citing works
Effects of Denervation on the Metabolism and the Response to Glucagon of White Adipose Tissue of Rats
Lefèbvre, P., LUYCKX, A. S., & Bacq, Z. M. (1973) · Hormone and Metabolic Research · doi:10.1055/s-0028-1093959 · Cited by 64 · see citing works
Modified metabolic responsiveness to glucagon in cold-acclimated and heat-acclimated rats
Doi, K., & KUROSHIMA, A. (1982) · Life Sciences · doi:10.1016/0024-3205(82)90614-2 · Cited by 63 · see citing works
Different Metabolic Responses in α-, β-, and δ-Cells of the Islet of Langerhans Monitored by Redox Confocal Microscopy
Quesada, I., Todorova, M. G., & Soria, B. (2006) · Biophysical Journal · doi:10.1529/biophysj.105.069906 · Cited by 63 · see citing works
Heterodimeric Pbx-Prep1 Homeodomain Protein Binding to the Glucagon Gene Restricting Transcription in a Cell Type-dependent Manner
Herzig, S., FÜZESI, L., & Knepel, W. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m003345200 · Cited by 60 · see citing works
Induction of ketogenesis and fatty acid oxidation by glucagon and cyclic AMP in cultured hepatocytes from rabbit fetuses. Evidence for a decreased sensitivity of carnitine palmitoyltransferase I to malonyl-CoA inhibition after glucagon or cyclic AMP treatment
Pégorier, J. P., Garcia-Garcia, M. V., Prip‐Buus, C., Duée, P., Kohl, C., & Girard, J. R. (1989) · Biochemical Journal · doi:10.1042/bj2640093 · Cited by 59 · see citing works
Protein hydrolysates stimulate proglucagon gene transcription in intestinal endocrine cells via two elements related to cyclic AMP response element
Gevrey, J., Body–Malapel, M., Philippé, J., Mithieux, G., Chayvialle, J. A., Abello, J., & Cordier–Bussat, M. (2004) · Diabetologia · doi:10.1007/s00125-004-1380-0 · Cited by 59 · see citing works
Effect of glucagon on the serum lipids in essential hyperlipemia and in hypercholesterolemia.
Ds, A., Grande, F., & WADA, S. (1962) · PubMed · Cited by 59 · see citing works
High‐fat diet‐induced hepatic steatosis reduces glucagon receptor content in rat hepatocytes: potential interaction with acute exercise
Charbonneau, A., Unson, C. G., & Lavoie, J.-M. (2006) · The Journal of Physiology · doi:10.1113/jphysiol.2006.121954 · Cited by 58 · see citing works
Hepatic portal infusion of glucagon antibodies increases spontaneous meal size in rats
Sauter, J. L., Noh, U., & Geary, N. (1991) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1991.261.1.r162 · Cited by 57 · see citing works
Self-citation
Human glucagon and vasoactive intestinal polypeptide (VIP) stimulate free fatty acid release from human adipose tissue in vitro
Richter, W. O., Robl, H., & SCHWANDT, P. (1989) · Peptides · doi:10.1016/0196-9781(89)90039-9 · Cited by 53 · see citing works
β-Cell–Mediated Signaling Predominates Over Direct α-Cell Signaling in the Regulation of Glucagon Secretion in Humans
Cooperberg, B. A., & Cryer, P. E. (2009) · Diabetes Care · doi:10.2337/dc09-0798 · Cited by 53 · see citing works
Insulin dissociates hepatic glucose cycling and glucagon-induced thermogenesis in man
Calles-Escandón, J. (1994) · Metabolism · doi:10.1016/0026-0495(94)90180-5 · Cited by 50 · see citing works
Apparent thermogenic effect of injected glucagon is not due to a direct effect on brown fat cells
Dicker, A., Zhao, J., Cannon, B., & Nedergaard, J. (1998) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1998.275.5.r1674 · Cited by 50 · see citing works
Hepatic handling of pancreatic glucagon and glucose during meals in rats
Langhans, W., Pantel, K., Muller-Schell, W., Eggenberger, E., & Scharrer, E. (1984) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1984.247.5.r827 · Cited by 50 · see citing works
The complex regulation of receptor-coupled G-proteins
Rodbell, M. (1997) · Advances in Enzyme Regulation · doi:10.1016/s0065-2571(96)00020-9 · Cited by 48 · see citing works
Differential expression of glucagon and glucagon-like peptide 1 receptors in mouse pancreatic alpha and beta cells in two models of alpha cell hyperplasia
Kedees, M. H., Grigoryan, M., Guz, Y., & Teitelman, G. (2009) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2009.07.024 · Cited by 44 · see citing works
Metabolic effects of glucagon in human subjects.
Salter, J., EZRIN, C., LAIDLAW, J. C., & Gornall, A. G. (1960) · PubMed · Cited by 43 · see citing works
Stimulatory short-term effects of free fatty acids on glucagon secretion at low to normal glucose concentrations
Bollheimer, L. C., Landauer, H. C., Troll, S., Schweimer, J., Wrede, C. E., Schölmerich, J., & Buettner, R. (2004) · Metabolism · doi:10.1016/j.metabol.2004.06.011 · Cited by 43 · 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
Glucagon as a regulating factor of plasma lipids.
Paloyan, E., & Harper, P. V. (1961) · PubMed · Cited by 42 · see citing works
Evidence of Hepatic Glucagon Resistance Associated with Hepatic Steatosis: Reversal Effect of Training
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
Hepatic portal glucagon infusion decreases spontaneous meal size in rats
Sauter, J. L., & Geary, N. (1991) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1991.261.1.r154 · Cited by 37 · see citing works
Self-citation
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
GLUCAGON RESISTANCE AS A HORMONAL BASIS FOR ENDOGENOUS HYPERLIPÆMIA
Eaton, R. P., & Schade, D. S. (1973) · The Lancet · doi:10.1016/s0140-6736(73)91605-x · Cited by 34 · see citing works
Glucagon and cholesterol metabolism.
Caren, R., & Corbo, L. (1960) · PubMed · Cited by 34 · 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
Regulation of fatty-acid metabolism by pancreatic hormones in cultured human hepatocytes
Vons, C., Pégorier, J. P., Girard, J. R., Kohl, C., Ivanov, M., & Franco, D. (1991) · Hepatology · doi:10.1002/hep.1840130620 · Cited by 32 · see citing works
Glucose Regulates Proinsulin and Prosomatostatin But Not Proglucagon Messenger Ribonucleic Acid Levels in Rat Pancreatic Islets1
Dumonteil, E., Magnan, C., Ritz-Laser, B., Ktorza, A., Meda, P., & Philippé, J. (2000) · Endocrinology · doi:10.1210/endo.141.1.7230 · Cited by 31 · see citing works
Effects of central administration of glucagon on feed intake and endocrine responses in sheep
Kurose, Y., Kamisoyama, H., Honda, K., AZUMA, Y., Sugahara, K., HASEGAWA, S., & Kobayashi, S. (2009) · Animal Science Journal · doi:10.1111/j.1740-0929.2009.00685.x · Cited by 29 · see citing works
Effect of chronic glucagon administration on lipoprotein composition in normally fed, fasted and cholesterol‐fed rats
Guettet, C., Rostaqui, N., Mathé, D., Lécuyer, B., Navarro, N., & JACOTOT, B. (1991) · Lipids · doi:10.1007/bf02536072 · Cited by 29 · see citing works
Effects of glucagon and noradrenaline on the blood flow through brown adipose tissue in temperature-acclimated rats.
Yahata, T., Habara, Y., & KUROSHIMA, A. (1983) · The Japanese Journal of Physiology · doi:10.2170/jjphysiol.33.367 · Cited by 29 · see citing works
Alterations in hepatic glucagon receptor density and in Gsα and Giα2protein content with diet-induced hepatic steatosis: effects of acute exercise
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
Role of glucagon on fatty liver production in birds
Oya, M. D., Prigge, W. F., Swenson, D., & Grande, F. (1971) · American Journal of Physiology-Legacy Content · doi:10.1152/ajplegacy.1971.221.1.25 · Cited by 27 · see citing works
Dose-related suppression of feeding by intraportal glucagon infusion in the rat
Weick, B. G., & Ritter, S. (1986) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1986.250.4.r676 · Cited by 25 · see citing works
Metabolic Responses of Lactating Dairy Cows to Single and Multiple Subcutaneous Injections of Glucagon
Bobe, G., Sonon, R. N., Ametaj, B. N., et al. (2003) · Journal of Dairy Science · doi:10.3168/jds.s0022-0302(03)73796-5 · Cited by 22 · see citing works
EFFECT OF GLUCAGON ON FOOD INTAKE AND WEIGHT GAIN IN THE YOUNG RAT
Holloway, S. A., & Stevenson, J. A. F. (1964) · Canadian Journal of Physiology and Pharmacology · doi:10.1139/y64-098 · Cited by 22 · see citing works
Role of catecholamines in glucagon-induced thermogenesis
Filali-Zegzouti, Y., Abdelmelek, H., Rouanet, J. L., et al. (2004) · Journal of Neural Transmission · doi:10.1007/s00702-004-0199-7 · Cited by 19 · 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
A role for protein kinase C-mediated phosphorylation in eliciting glucagon desensitization in rat hepatocytes
Savage, A., Zeng, L., & Houslay, M. D. (1995) · Biochemical Journal · doi:10.1042/bj3070281 · Cited by 19 · see citing works
Adaptive changes in insulin and glucagon secretion during cold acclimation in the rat
Edwards, C. I., & Howland, R. J. (1986) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1986.250.6.e669 · Cited by 17 · see citing works
Transfer of plasma lipid to platelets by action of glucagon
Caren, R., & Corbo, L. (1970) · Metabolism · doi:10.1016/0026-0495(70)90016-8 · Cited by 16 · see citing works
Effect of Chronic Glucagon Administration on the Metabolism of Triacylglycerol-Rich Lipoproteins in Rats Fed a High Sucrose Diet
Guettet, C., Rostaqui, N., Navarro, N., Lécuyer, B., & Mathé, D. (1991) · Journal of Nutrition · doi:10.1093/jn/121.1.24 · Cited by 15 · see citing works
Suppression by Hepatectomy of Glucagon-Induced Hypertriglyceridemia in Geese
de Oya, M., Prigge, W. F., & Grande, F. (1971) · Experimental Biology and Medicine · doi:10.3181/00379727-136-35205 · Cited by 10 · see citing works
Glucagon Effects on Ischemic Vasodilatation in the Isolated Rat Heart
Rosic, M. A., Pantović, S., Rosic, G. L., Lucic, A. T., Labudović, T., Zivkovic, V. I., & Jakovljevic, V. L. (2010) · BioMed Research International · doi:10.1155/2010/231832 · Cited by 9 · see citing works
Sympathetic control of glucagon receptor mRNA levels in brown adipose tissue of cold-exposed rats
Morales, A., Lachuer, J., Géoën, A., Georges, B., Duchamp, C., & Barré, H. (2000) · Molecular and Cellular Biochemistry · doi:10.1023/a:1007058525309 · Cited by 7 · see citing works
Glucagon and plasma arachidonic acid
Caren, R., & Corbo, L. (1965) · Metabolism · doi:10.1016/0026-0495(65)90051-x · Cited by 5 · see citing works

Flagged first, then by citations

Sorted by citations

A rationally designed monomeric peptide triagonist corrects obesity and diabetes in rodents
Finan, B., Yang, B., Ottaway, N., Smiley, D. L., Ma, T., Clemmensen, C., Chabenne, J., Zhang, L., Habegger, K. M., Fischer, K., et al. (2015) · Nature Medicine · doi:10.1038/nm.3761 · Cited by 645 · see citing works
Self-citation
Sex differences in the physiology of eating
Asarian, L., & Geary, N. (2013) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00446.2012 · Cited by 513 · see citing works
Self-citation
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
The New Biology and Pharmacology of Glucagon
Müller, T. D., Finan, B., Clemmensen, C., DiMarchi, R. D., & Tschöp, M. H. (2017) · Physiological Reviews · doi:10.1152/physrev.00025.2016 · Cited by 419 · see citing works
Self-citation
Effects of Cotadutide on Metabolic and Hepatic Parameters in Adults With Overweight or Obesity and Type 2 Diabetes: A 54-Week Randomized Phase 2b Study
Nahra, R., Wang, T., Gadde, K. M., Oscarsson, J., Stumvoll, M., Jermutus, L., Hirshberg, B., & Ambery, P. (2021) · Diabetes Care · doi:10.2337/dc20-2151 · Cited by 323 · see citing works
What is the pipeline for future medications for obesity?
Melson, E., Ashraf, U., Papamargaritis, D., & Davies, M. J. (2025) · International Journal of Obesity · doi:10.1038/s41366-024-01473-y · Cited by 332 · see citing works
“Glucagon is secreted from the pancreatic a-cells and the main physiological site of action is the liver to increase hepatic glucose production [60].”
LY3437943, a novel triple glucagon, GIP, and GLP-1 receptor agonist for glycemic control and weight loss: From discovery to clinical proof of concept.
Coskun, T., Urva, S., Roell, W. C., Qu, H., Loghin, C., Moyers, J. S., O’Farrell, L. S., Briere, D. A., Sloop, K. W., Thomas, M. K., et al. (2022) · Cell Metabolism · doi:10.1016/j.cmet.2022.07.013 · Cited by 316 · see citing works
Inter-organ cross-talk in metabolic syndrome
Priest, C., & Tontonoz, P. (2019) · Nature Metabolism · doi:10.1038/s42255-019-0145-5 · Cited by 279 · see citing works
Islet 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
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
Self-citation
Robust anti‐obesity and metabolic effects of a dual <scp>GLP</scp> ‐1/glucagon receptor peptide agonist in rodents and non‐human primates
Henderson, S. J., Konkar, A., Hornigold, D. C., Trevaskis, J. L., Jackson, R., Fritsch Fredin, M., Jansson‐Löfmark, R., Naylor, J., Rossi, A., Bednarek, M. A., et al. (2016) · Diabetes, Obesity and Metabolism · doi:10.1111/dom.12735 · Cited by 240 · see citing works
Action and therapeutic potential of oxyntomodulin
Pocai, A. (2014) · Molecular Metabolism · doi:10.1016/j.molmet.2013.12.001 · Cited by 191 · see citing works
Chemical Hybridization of Glucagon and Thyroid Hormone Optimizes Therapeutic Impact for Metabolic Disease
Finan, B., Clemmensen, C., Zhu, Z., Stemmer, K., Gauthier, K., Müller, L., De Angelis, M., Moreth, K., Neff, F., Perez-Tilve, D., et al. (2016) · Cell · doi:10.1016/j.cell.2016.09.014 · Cited by 191 · see citing works
Self-citation
GLP-1/glucagon receptor co-agonism for treatment of obesity
Sánchez-Garrido, M. A., Brandt, S. J., Clemmensen, C., Müller, T. D., DiMarchi, R. D., & Tschöp, M. H. (2017) · Diabetologia · doi:10.1007/s00125-017-4354-8 · Cited by 175 · see citing works
Self-citation
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
Self-citation
Efficacy and Safety of Tirzepatide in Type 2 Diabetes and Obesity Management
Sinha, R., Papamargaritis, D., Sargeant, J. A., & Davies, M. J. (2023) · Journal of Obesity & Metabolic Syndrome · doi:10.7570/jomes22067 · Cited by 138 · see citing works
Optimization of co-agonism at GLP-1 and glucagon receptors to safely maximize weight reduction in DIO-rodents
Day, J. W., Gelfanov, V., Smiley, D., Carrington, P. E., Eiermann, G., Chicchi, G., Erion, M. D., Gidda, J., Thornberry, N. A., Tschöp, M. H., et al. (2012) · Peptide Science · doi:10.1002/bip.22072 · Cited by 133 · see citing works
Self-citation
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
A novel glucagon-like peptide-1 (GLP-1)/Glucagon hybrid peptide with triple-acting agonist activity at glucose-dependent insulinotropic polypeptide, GLP-1, and glucagon receptors and therapeutic potential in high fat-fed mice
Gault, V. A., Bhat, V. K., Irwin, N., & Flatt, P. R. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.512046 · Cited by 123 · see citing works
Efficacy, safety, and mechanistic insights of cotadutide, a dual receptor glucagon-like peptide-1 and glucagon agonist
Parker, V. E. R., Robertson, D., Wang, T., Hornigold, D. C., Petrone, M., Cooper, A. T., Posch, M. G., Heise, T., Plum-Moerschel, L., Schlichthaar, H., et al. (2020) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgz047 · Cited by 123 · 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
Allostery and biased agonism at class B G protein-coupled receptors
Wootten, D., Miller, L. J., Koole, C., Christopoulos, A., & Sexton, P. M. (2017) · Chemical Reviews · doi:10.1021/acs.chemrev.6b00049 · Cited by 112 · see citing works
Selective slow wave sleep but not rapid eye movement sleep suppression impairs morning glucose tolerance in healthy men
Herzog, N., Jauch-Chara, K., Hyzy, F., Richter, A., Friedrich, A., Benedict, C., & Oltmanns, K. M. (2013) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2013.03.018 · Cited by 100 · see citing works
Design of Novel Exendin-Based Dual Glucagon-like Peptide 1 (GLP-1)/Glucagon Receptor Agonists
Evers, A., Haack, T., Lorenz, M., Bossart, M., Elvert, R., Henkel, B., Stengelin, S., Kurz, M., Glien, M., Dudda, A., et al. (2017) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.7b00174 · Cited by 101 · see citing works
Glucagon Receptor Blockade With a Human Antibody Normalizes Blood Glucose in Diabetic Mice and Monkeys
Okamoto, 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
Multi-omics analysis of multiple missions to space reveal a theme of lipid dysregulation in mouse liver
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
Glucagon Receptor Signaling Regulates Energy Metabolism via Hepatic Farnesoid X Receptor and Fibroblast Growth Factor 21
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-citation
Striking the balance: GLP-1/glucagon co-agonism as a treatment strategy for obesity
Hope, D. C. D., Vincent, M. L., & Tan, T. M. M. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.735019 · Cited by 81 · see citing works
New therapies for obesity
Papamargaritis, D., le Roux, C. W., Holst, J. J., & Davies, M. J. (2024) · Cardiovascular Research · doi:10.1093/cvr/cvac176 · Cited by 73 · see citing works
Dual and Triple Incretin-Based Co-agonists: Novel Therapeutics for Obesity and Diabetes
Gutgesell, R. M., Nogueiras, R., Tschöp, M. H., & Müller, T. D. (2024) · Diabetes Therapy · doi:10.1007/s13300-024-01566-x · Cited by 61 · see citing works
“Therefore, glucagon acts not only to increase glucose production but also to induce lipolysis, fatty acid oxidation, ketogene-sis, increase thermogenesis and energy expenditure, bile acid synthesis, and finally induce satiation and reduce food intake [22, 23].”
BackgroundSelf-citation
Improved postprandial glucose metabolism in type 2 diabetes by the dual glucagon-like peptide-1/glucagon receptor agonist SAR425899 in comparison with liraglutide
Schiavon, M., Visentin, R., Göbel, B., Riz, M., Cobelli, C., Klabunde, T., & Dalla Man, C. (2021) · Diabetes, Obesity and Metabolism · doi:10.1111/dom.14394 · Cited by 49 · see citing works
GLP-1 receptor agonist-based therapies and cardiovascular risk: a review of mechanisms
Mullur, N., Morissette, A., Morrow, N. M., & Mulvihill, E. E. (2024) · Journal of Endocrinology · doi:10.1530/joe-24-0046 · Cited by 51 · see citing works
Future therapies for obesity
Melson, E., Miras, A. D., & Papamargaritis, D. (2023) · Clinical Medicine · doi:10.7861/clinmed.2023-0144 · Cited by 46 · see citing works
Effects of multiple ascending doses of the glucagon receptor antagonist <scp>PF</scp> ‐06291874 in patients with type 2 diabetes mellitus
Kazierad, D. J., Bergman, A., Tan, B., Erion, D. M., Somayaji, V., Lee, D. S., & Rolph, T. (2016) · Diabetes, Obesity and Metabolism · doi:10.1111/dom.12672 · Cited by 44 · see citing works
Results from three phase 1 trials of NNC9204-1177, a glucagon/GLP-1 receptor co-agonist: Effects on weight loss and safety in adults with overweight or obesity
Friedrichsen, M. H., Endahl, L., Kreiner, F. F., Goldwater, R., Kankam, M., Toubro, S., & Nygård, S. B. (2023) · Molecular Metabolism · doi:10.1016/j.molmet.2023.101801 · Cited by 46 · see citing works
“Beyond the role of glucagon in glucose homeostasis, there are additional metabolic effects; these include increasing satiety and reducing food intake, as well as effects on lipid homeostasis and the increase of energy expenditure [8,9].”
Background
Is Glucagon Receptor Activation the Thermogenic Solution for Treating Obesity?
Conceição-Furber, E., Coskun, T., Sloop, K. W., & Samms, R. J. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.868037 · Cited by 48 · see citing works
Glucagon in type 2 diabetes: Friend or foe?
Caruso, I., Marrano, N., Biondi, G., Genchi, V. A., D'Oria, R., Sorice, G. P., Perrini, S., Cignarelli, A., Natalicchio, A., Laviola, L., et al. (2023) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.3609 · Cited by 35 · see citing works
Glucagon agonism in the treatment of metabolic diseases including type 2 diabetes mellitus and obesity
Winther, J. B., & Holst, J. J. (2024) · Diabetes, Obesity and Metabolism · doi:10.1111/dom.15693 · Cited by 47 · see citing works
The promise of glucagon-like peptide 1 receptor agonists (GLP-1RA) for the treatment of obesity: a look at phase 2 and 3 pipelines
Madsbad, S., & Holst, J. J. (2025) · Expert Opinion on Investigational Drugs · doi:10.1080/13543784.2025.2472408 · Cited by 43 · see citing works
“This combination is of interest because here the GLP-1 effects are combined with the effects of glucagon in the liver with stimulation of beta-oxidation of lipids and inhibition of de novo lipogenesis in the liver [99,100].”
Influential
Preclinical evaluation of a protracted GLP-1/glucagon receptor co-agonist: translational difficulties and pitfalls
Simonsen, L., Lau, J., Kruse, T., Guo, T., McGuire, J., Jeppesen, J. F., Niss, K., Sauerberg, P., Raun, K., & Dornonville de la Cour, C. (2022) · PLOS ONE · doi:10.1371/journal.pone.0264974 · Cited by 36 · see citing works
Cracking the combination: Gut hormones for the treatment of obesity and diabetes
Alexiadou, K., Anyiam, O., & Tan, T. (2019) · Journal of Neuroendocrinology · doi:10.1111/jne.12664 · Cited by 34 · see citing works
Naturally occurring mutations in G protein-coupled receptors associated with obesity and type 2 diabetes mellitus
Liu, T., Ji, R.-L., & Tao, Y.-X. (2022) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2021.108044 · Cited by 34 · see citing works
Novel GLP-1-based Medications for Type 2 Diabetes and Obesity
Son, J. W., le Roux, C. W., Blüher, M., Nauck, M. A., & Lim, S. (2026) · Endocrine Reviews · doi:10.1210/endrev/bnaf036 · Cited by 33 · see citing works
<scp>Glucagon‐like peptide</scp> ‐1/glucagon receptor agonism associates with reduced metabolic adaptation and higher fat oxidation: A randomized trial
Corbin, K. D., Carnero, E. A., Allerton, T. D., Tillner, J., Bock, C. P., Luyet, P., Göbel, B., Hall, K. D., Parsons, S. A., Ravussin, E., et al. (2023) · Obesity · doi:10.1002/oby.23633 · Cited by 32 · see citing works
A GLP‐1/glucagon (GCG)/CCK<sub>2</sub> receptors tri‐agonist provides new therapy for obesity and diabetes
Zhao, S., Yan, Z., Du, Y., Li, Z., Tang, C., Jing, L., Sun, L., Yang, Q., Tang, X., Yuan, Y., et al. (2022) · British Journal of Pharmacology · doi:10.1111/bph.15860 · Cited by 30 · see citing works
Investigational glucagon-like peptide-1 agonists for the treatment of obesity
Tomlinson, B., Hu, M., Zhang, Y., Chan, P., & Liu, Z.-M. (2016) · Expert Opinion on Investigational Drugs · doi:10.1080/13543784.2016.1221925 · Cited by 25 · see citing works
Triple Agonism Based Therapies for Obesity
Goldney, J., Hamza, M., Surti, F., Davies, M. J., & Papamargaritis, D. (2025) · Current Cardiovascular Risk Reports · doi:10.1007/s12170-025-00770-z · Cited by 22 · see citing works
Comparison of the Effects of Liraglutide, Tirzepatide, and Retatrutide on Diabetic Kidney Disease in Db/Db Mice
Ma, J., Hu, X., Zhang, W., Tao, M., Wang, M., & Lu, W. (2024) · Endocrine · doi:10.1007/s12020-024-03998-8 · Cited by 21 · see citing works
An updated patent review of GLP-1 receptor agonists (2020-present)
Lu, W., Zhou, Z., Jiang, N., & Han, J. (2023) · Expert Opinion on Therapeutic Patents · doi:10.1080/13543776.2023.2274905 · Cited by 17 · see citing works
Higher endogenous glucose production during OGTT vs isoglycemic intravenous glucose infusion
Lund, A., Bagger, J. I., Christensen, M., Grøndahl, M., van Hall, G., Holst, J. J., Vilsbøll, T., & Knop, F. K. (2016) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2016-1948 · Cited by 12 · see citing works

Metabolic impact of glucagon deficiency
Hayashi, Y. (2011) · Diabetes Obesity and Metabolism · doi:10.1111/j.1463-1326.2011.01456.x · Cited by 31 · 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
Hepatic glucagon receptor binding and glucose-lowering in vivo by peptidyl and non-peptidyl glucagon receptor antagonists
Dallas-Yang, Q., Shen, X., Strowski, M. Z., Brady, E. J., Saperstein, R., Gibson, R. E., Szalkowski, D., Qureshi, S. A., Candelore, M. R., Fenyk-Melody, J. E., et al. (2004) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2004.08.023 · Cited by 40 · see citing works
Glucagon receptor blockage inhibits β-cell dedifferentiation through FoxO1
Wang, K., Cui, X., Li, F., Li, X., Wei, T., Liu, J., Fu, W., Yang, J., Hong, T., & Wei, R. (2022) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00101.2022 · Cited by 11 · see citing works
100 years of glucagon and 100 more
Wewer Albrechtsen, N. J., Holst, J. J., Cherrington, A. D., Finan, B., Gluud, L. L., Dean, E. D., Campbell, J. E., Bloom, S. R., Tan, T. M.-M., Knop, F. K., et al. (2023) · Diabetologia · doi:10.1007/s00125-023-05947-y · Cited by 117 · see citing works

Authors: Habegger, K. M., Heppner, K. M., Geary, N., Bartness, T. J., DiMarchi, R., & Tschöp, M. H.
Affiliations: University of Cincinnati (US)
ETH Zurich (CH)
Georgia State University (US)
Indiana University Bloomington (US)
Corresponding author: Tschöp, Matthias H.
ORCID: Habegger, Kirk M.
Geary, Nori
Bartness, Timothy J.
DiMarchi, Richard
Tschöp, Matthias H.
Venue: Nature Reviews Endocrinology
Publisher: Springer Science and Business Media LLC
Published: 2010-10-19
Volume: 6
Issue: 12
Pages: 689-697
ISSN: 1759-5029 (ISSN-L)
1759-5037
DOI: 10.1038/nrendo.2010.187
PMC: PMC3563428
OpenAlex: W2068226015
Cited by: 406
References: 129
Citations by year: 2026: 20 · 2025: 33 · 2024: 36 · 2023: 47 · 2022: 36 · 2021: 35 · 2020: 21 · 2019: 37 · 2018: 26 · 2017: 22 · 2016: 23 · 2015: 20 · 2014: 14 · 2013: 21 · 2012: 10
FWCI: 1.16
Type: journal article
Language: en
Open access: green
europepmc.org
Licence: www.springer.com/tdm (tdm)
Locations: Nature Reviews Endocrinology (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Site cant be reached (submittedVersion)
Funders: National Institutes of Health (5r01dk077975-05)
National Institute of Diabetes and Digestive and Kidney Diseases (R01-DK-077975)
Topics: Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
Keywords: glucagon, GLP-1 receptor, insulin, lipid metabolism, energy balance, energy expenditure, satiety, anti-obesity, dyslipidemia, obesity, metabolic syndrome, adipose tissue mass, dietary intake
MeSH terms: Adipose Tissue, Animals, Energy Metabolism, Glucagon, Humans, Metabolism, Models, Biological, Obesity, Lipid Metabolism

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

The metabolic actions of glucagon revisited

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Self-check

Cites

Cited by

Related

Record

About these checks