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Glucagon receptor knockout mice are resistant to diet-induced obesity and streptozotocin-mediated beta cell loss and hyperglycaemia
Open accessAbstract
Aims/hypothesis Under normal physiological conditions, glucagon signalling is important in glucose homeostasis. Hyperglucagonaemia or altered insulin:glucagon ratio plays a role in maintaining hyperglycaemia in subjects with type 2 diabetes. It has been reported that glucagon receptor knockout (Gcgr (-/-)) mice develop normally and have lower plasma glucose on a normal diet. The goal of the current research was to further investigate the role of glucagon signalling in metabolic control and glucose homeostasis.Methods Gcgr (-/-) mice were challenged with a high-fat diet (HFD) and with streptozotocin, which induces beta cell damage. They were then analysed for whole-body and serum metabolic phenotypes as well as pancreatic islet morphology.Results In comparison with wild-type mice, Gcgr (-/-) mice exhibited decreased body weight and food intake, reduced plasma glucose levels, and improved oral and intraperitoneal glucose tolerance. Elevated glucagon-like peptide-1 levels and reduced gastric emptying were also observed in Gcgr (-/-) mice, which also had reduced HFD-induced hyperinsulinaemia and hyperleptinaemia, and were resistant to the development of hepatic steatosis. In addition, Gcgr (-/-) mice were resistant to STZ-induced hyperglycaemia and pancreatic beta cell destruction.Conclusions/interpretation This study demonstrates that blocking glucagon signalling by targeted Gcgr gene deletion leads to an improvement in metabolic control in this mouse model.
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“While lack of GCGR signaling can normalize glycemia under insulin-deficient conditions15,16, this effect is contingent on the presence of residual insulin17.”
From Transforming obesity: The advancement of multi-receptor drugs (2024) · cites this paper as [15]
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Cites
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
Self-citationGelling, 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-citationMinireview: The Glucagon-Like Peptides
Drucker, D. J. (2001) · Endocrinology · doi:10.1210/endo.142.2.7983 · Cited by 419
EFFECT OF EPINEPHRINE ON RAT DIAPHRAGM
Walaas, O., & Walaas, E. (1950) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)56223-2 · Cited by 410
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
Glucagon physiology and pathophysiology in the light of new advances
Unger, R. H. (1985) · Diabetologia · doi:10.1007/bf00281991 · Cited by 361
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 348
Self-citationPospisilik, 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
Sloop, K. W., Cao, J. X. C., Siesky, A. M., Zhang, H. Y., Bodenmiller, D. M., Cox, A. L., Jacobs, S. J., Moyers, J. S., Owens, R. A., Showalter, A. D., et al. (2004) · Journal of Clinical Investigation · doi:10.1172/jci20911 · Cited by 219
Petersen, K. F., & Sullivan, J. T. (2001) · Diabetologia · doi:10.1007/s001250100006 · Cited by 212
Role of Liver in Pathophysiology of NIDDM
Consoli, A. (1992) · Diabetes Care · doi:10.2337/diacare.15.3.430 · Cited by 210
Liang, Y. T., Osborne, M. C., Monia, B. P., Bhanot, S., Gaarde, W. A., Reed, C. A., She, P., Jetton, T. L., & Demarest, K. T. (2004) · Diabetes · doi:10.2337/diabetes.53.2.410 · Cited by 202
New approaches in the treatment of type 2 diabetes
Zhang, B. B., & Moller, D. E. (2000) · Current Opinion in Chemical Biology · doi:10.1016/s1367-5931(00)00103-4 · Cited by 196
Self-citationHyperglycemia of Diabetic Rats Decreased by a Glucagon Receptor Antagonist
Johnson, D. G., Goebel, C. U., Hruby, V. J., Bregman, M. D., & Trivedi, D. B. (1982) · Science · doi:10.1126/science.6278587 · Cited by 166
Glycemic Control in Mice with Targeted Disruption of the Glucagon Receptor Gene
Parker, J. C., Andrews, K. M., Allen, M. R., Stock, J. L., & McNeish, J. D. (2002) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2001.6265 · Cited by 160
Glucagon-like peptide 1 (GLP-1) as a new therapeutic approach for Type 2-diabetes
Nauck, M. A., Holst, J. J., Willms, B., & Schmiegel, W. (2009) · Experimental and Clinical Endocrinology & Diabetes · doi:10.1055/s-0029-1211750 · Cited by 145
Brand, C. L., Rolin, B., Jørgensen, P. N., Svendsen, I., Kristensen, J. S., & Holst, J. J. (1994) · Diabetologia · doi:10.1007/bf00400461 · Cited by 135
Butler, P. C., & Rizza, R. A. (1991) · Diabetes · doi:10.2337/diab.40.1.73 · Cited by 127
Biological activities of des-His1[Glu9]glucagon amide, a glucagon antagonist
Unson, C. G., Gurzenda, E. M., & Merrifield, R. B. (1989) · Peptides · doi:10.1016/0196-9781(89)90010-7 · Cited by 119
D’Alessio, D. A., Vogel, R., Prigeon, R. L., Laschansky, E. C., Koerker, D. J., Eng, J., & Ensinck, J. W. (1996) · Journal of Clinical Investigation · doi:10.1172/jci118380 · Cited by 119
A Novel Glucagon Receptor Antagonist Inhibits Glucagon-Mediated Biological Effects
Qureshi, S. A., Candelore, M. R., Xie, D., Yang, X., Tota, L. M., Ding, V. D. H., Li, Z., Bansal, A., Miller, C. O., Cohen, S. M., et al. (2004) · Diabetes · doi:10.2337/diabetes.53.12.3267 · Cited by 109
Self-citationLarsson, H. E., & Åhrén, B. (2000) · Diabetes Care · doi:10.2337/diacare.23.5.650 · Cited by 98
Brand, C. L., Jørgensen, P. N., Svendsen, I., & Holst, J. J. (1996) · Diabetes · doi:10.2337/diab.45.8.1076 · Cited by 94
Molecular and cellular aspects of the glucagon receptor: role in diabetes and metabolism.
Burcelin, R., Katz, E. B., & Charron, M. J. (1996) · PubMed · Cited by 93
Self-citationBasu, A., Alzaid, A., Dinneen, S. F., Caumo, A., Cobelli, C., & Rizza, R. A. (1996) · Journal of Clinical Investigation · doi:10.1172/jci118678 · Cited by 90
Fujita, Y., Kojima, H., Hidaka, H., Fujimiya, M., Kashiwagi, A., & Kikkawa, R. (1998) · Diabetologia · doi:10.1007/s001250051092 · Cited by 88
Role of glucagon in maintenance of euglycemia in fed and fasted rats
Brand, C. L., Jørgensen, P. N., Knigge, U., Warberg, J., Svendsen, I., Kristensen, J. S., & Holst, J. J. (1995) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1995.269.3.e469 · Cited by 77
Alleviation of Fatty Liver in Dairy Cows with 14-Day Intravenous Infusions of Glucagon
Hippen, A. R., She, P., Young, J. W., Beitz, D. C., Lindberg, G. L., Richardson, L. F., & Tucker, R. W. (1999) · Journal of Dairy Science · doi:10.3168/jds.s0022-0302(99)75337-3 · Cited by 60
Identification of Alkylidene Hydrazides as Glucagon Receptor Antagonists
Ling, A. L., Hong, Y., González, J., Gregor, V. E., Polinsky, A., Kuki, A., Shi, S., Teston, K., Murphy, D. E., Porter, J. W., et al. (2001) · Journal of Medicinal Chemistry · doi:10.1021/jm000547o · Cited by 42
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
Self-citationHuman glucagon receptor antagonists based on alkylidene hydrazides
Ling, A. L., Plewe, M. B., González, J., Madsen, P., Sams, C. K., Lau, J. F., Gregor, V. E., Murphy, D., Teston, K., Kuki, A., et al. (2002) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/s0960-894x(01)00819-8 · Cited by 40
Discovery of novel, potent, and orally active spiro-urea human glucagon receptor antagonists
Shen, D., Zhang, F., Brady, E. J., Candelore, M. R., Dallas-Yang, Q., Ding, V. D. H., Dragovic, J., Feeney, W. P., Jiang, G., McCann, P. E., et al. (2005) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2005.06.101 · Cited by 40
Self-citationNakade, Y., Tsukamoto, K., Pappas, T. N., & Takahashi, T. (2006) · Brain Research · doi:10.1016/j.brainres.2006.06.090 · Cited by 37
Tine, B. A. V., Azizeh, B. Y., Trivedi, D., Phelps, J. R., Houslay, M. D., Johnson, D. G., & Hruby, V. J. (1996) · Endocrinology · doi:10.1210/endo.137.8.8754757 · Cited by 36
Harnessing the Therapeutic Potential of Glucagon-Like Peptide-1
Baggio, L. L., & Drucker, D. J. (2002) · Treatments in Endocrinology · doi:10.2165/00024677-200201020-00005 · Cited by 35
Ehrenpreis, E. D., Salvino, M. J., & Craig, R. M. (2001) · Journal of Clinical Gastroenterology · doi:10.1097/00004836-200107000-00009 · Cited by 20
Glucagon as a Potential Therapy for Ketosis and Fatty Liver
Hippen, A. R. (2000) · Veterinary Clinics of North America Food Animal Practice · doi:10.1016/s0749-0720(15)30105-5 · Cited by 19
Autoregulation of endogenous glucose production during hyperglucagonemia
Toft, I., Gerich, J. E., & Jenssen, T. G. (2002) · Metabolism · doi:10.1053/meta.2002.34702 · Cited by 18
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Rui, L. (2014) · Comprehensive physiology · doi:10.1002/cphy.c130024 · Cited by 2,401
Emerging Targets in Type 2 Diabetes and Diabetic Complications
Demir, S., Nawroth, P. P., Herzig, S., & Üstünel, B. E. (2021) · Advanced Science · doi:10.1002/advs.202100275 · Cited by 582
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
Hormonal regulation of hepatic glucose production in health and disease
Lin, H. V., & Accili, D. (2011) · Cell Metabolism · doi:10.1016/j.cmet.2011.06.003 · Cited by 429
The metabolic actions of glucagon revisited
Habegger, K. M., Heppner, K. M., Geary, N., Bartness, T. J., DiMarchi, R., & Tschöp, M. H. (2010) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2010.187 · Cited by 406
Metadata
- Authors
- Conarello, S. L., Jiang, G., Mu, J., Li, Z., Woods, J., Zycband, E., Ronan, J., Liu, F., Roy, R. S., Zhu, L., Charron, M. J., & Zhang, B. B.
- Affiliations
- Merck & Co., Inc., Rahway, NJ, USA (United States) (US)
- Albert Einstein College of Medicine (US)
- Corresponding author
- Zhang, B. B.
- Venue
- Diabetologia
- Published
- 2006-11-28
- Volume
- 50
- Issue
- 1
- Pages
- 142-150
- ISSN
- 0012-186X (ISSN-L)
- 1432-0428
- OpenAlex
- W1988784323
- Cited by
- 224
- References
- 38
- Citations by year
- 2026: 5 · 2025: 6 · 2024: 12 · 2023: 7 · 2022: 16 · 2021: 15 · 2020: 10 · 2019: 17 · 2018: 17 · 2017: 10 · 2016: 16 · 2015: 17 · 2014: 17 · 2013: 9 · 2012: 14
- FWCI
- 4.74
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Diabetologia (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Keywords
- glucagon receptor, glucose homeostasis, diet-induced obesity, high-fat diet, beta cell destruction, hyperglycemia, insulin/glucagon ratio, glucagon-like peptide-1, gastric emptying, hepatic steatosis, hyperinsulinemia, leptin, type 2 diabetes
- MeSH terms
- Animals, Diabetes Mellitus, Experimental, Dietary Fats, Disease Models, Animal, Glucose, Homeostasis, Hyperglycemia, Male, Mice, Inbred C57BL, Obesity, Streptozocin, Apoptosis, Gene Deletion, Receptors, Glucagon, Mice, Knockout, Insulin-Secreting Cells, Mice
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