The DOI matches its Crossref record; 47 of the 47 references it cites were found in a registry or an index.
The Glucagon Receptor Is Required for the Adaptive Metabolic Response to Fasting
Open accessAbstract
Glucagon receptor (Gcgr) signaling maintains hepatic glucose production during the fasting state; however, the importance of the Gcgr for lipid metabolism is unclear. We show here that fasted Gcgr-/- mice exhibit a significant increase in hepatic triglyceride secretion and fasting increases fatty acid oxidation (FAO) in wild-type (WT) but not in Gcgr-/- mice. Moreover fasting upregulated the expression of FAO-related hepatic mRNA transcripts in Gcgr+/+ but not in Gcgr-/- mice. Exogenous glucagon administration reduced plasma triglycerides in WT mice, inhibited TG synthesis and secretion, and stimulated FA beta oxidation in Gcgr+/+ hepatocytes. The actions of glucagon on TG synthesis and FAO were abolished in PPARalpha-/- hepatocytes. These findings demonstrate that the Gcgr receptor is required for control of lipid metabolism during the adaptive metabolic response to fasting.
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“Based on these findings, activation of the glucagon receptor may have a favorable effect on the development and treatment of MAFLD, commonly seen in T2DM.”
From New Developments in Pharmacological Treatment of Obesity and Type 2 Diabetes—Beyond and within GLP-1 Receptor Agonists (2024) · cites this paper as [66]
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“In addition to its blood glucose-increasing effect, glucagon activates fat breakdown and inhibits lipogenesis in the liver, reducing concentrations of non-esterified fatty acids and triacylglycerol, and moderating triglyceride content in liver cells in animal experiments [66].”
From New Developments in Pharmacological Treatment of Obesity and Type 2 Diabetes—Beyond and within GLP-1 Receptor Agonists (2024) · cites this paper as [66]
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Citations
Cites
Peroxisome proliferator–activated receptor α mediates the adaptive response to fasting
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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 1,026
Sorting out the roles of PPAR in energy metabolism and vascular homeostasis
Lefebvre, P. (2006) · Journal of Clinical Investigation · doi:10.1172/jci27989 · Cited by 962
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
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
Self-citationADD1/SREBP-1c Is Required in the Activation of Hepatic Lipogenic Gene Expression by Glucose
Foretz, M., Pacot, C., Dugail, I., Lemarchand, P., Guichard, C., Lièpvre, X. L., Lubrano-Berthelier, C., Spiegelman, B. M., Kim, J. B., Ferré, P., et al. (1999) · Molecular and Cellular Biology · doi:10.1128/mcb.19.5.3760 · Cited by 548
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 514
Self-citationExpression cloning and signaling properties of the rat glucagon receptor
Jelinek, L., Lok, S., Rosenberg, G., Smith, R., Grant, F., BIGGS, S., Bensch, P., Kuijper, J. L., Sheppard, P. O., Sprecher, C. A., et al. (1993) · Science · doi:10.1126/science.8384375 · Cited by 397
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Energy Metabolism in the Liver
Rui, L. (2014) · Comprehensive physiology · doi:10.1002/cphy.c130024 · Cited by 2,401
Regulation of hepatic glucose metabolism in health and disease
Petersen, M. C., Vatner, D. F., & Shulman, G. I. (2017) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2017.80 · Cited by 1,159
Metabolism disrupting chemicals and metabolic disorders
Heindel, J. J., Blumberg, B., Cave, M., Machtinger, R., Mantovani, A., Mendez, M. A., Nadal, A., Palanza, P., Panzica, G., Sargis, R., et al. (2017) · Reproductive Toxicology · doi:10.1016/j.reprotox.2016.10.001 · Cited by 1,101
Mechanisms of hepatic triglyceride accumulation in non-alcoholic fatty liver disease
Kawano, Y., & Cohen, D. E. (2013) · Journal of Gastroenterology · doi:10.1007/s00535-013-0758-5 · Cited by 1,009
Potthoff, M. J., Inagaki, T., Satapati, S., Ding, X., He, T., Goetz, R., Mohammadi, M., Finck, B. N., Mangelsdorf, D. J., Kliewer, S. A., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0904187106 · Cited by 704
Metadata
- Authors
- Longuet, C., Sinclair, E. M., Maida, A., Baggio, L. L., Maziarz, M., Charron, M. J., & Drucker, D. J.
- Affiliations
- Mount Sinai Hospital (CA)
- Albert Einstein College of Medicine (US)
- Corresponding author
- Drucker, Daniel J.
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2008-11
- Volume
- 8
- Issue
- 5
- Pages
- 359-371
- ISSN
- 1550-4131 (ISSN-L)
- PMC
- PMC2593715
- OpenAlex
- W2085330452
- Cited by
- 272
- References
- 47
- Citations by year
- 2026: 14 · 2025: 16 · 2024: 23 · 2023: 17 · 2022: 17 · 2021: 16 · 2020: 17 · 2019: 14 · 2018: 10 · 2017: 20 · 2016: 10 · 2015: 19 · 2014: 18 · 2013: 12 · 2012: 20
- FWCI
- 3.98
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Funders
- Canadian Institutes of Health Research (10903)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK047425, R01DK47425)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Keywords
- glucagon receptor, fasting, hepatic lipid metabolism, fatty acid oxidation, hepatic triglyceride secretion, triglyceride synthesis, PPARα, glucagon, hepatic glucose production
- MeSH terms
- Adaptation, Biological, Animals, Cells, Cultured, Fasting, Fatty Acids, Female, Glucagon, Male, Oxidation-Reduction, RNA, Messenger, Triglycerides, Receptors, Glucagon, Mice, Knockout, Hepatocytes, PPAR alpha, p38 Mitogen-Activated Protein Kinases, Lipid Metabolism, Mice, AMP-Activated Protein Kinases
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