Glucagon and Oxyntomodulin, a peptide hormone secreted by the alpha cells of pancreas, share identical amino acid sequence in the N-terminal 29 aa. Glucagon is a 29-amino acid polypeptide processed from proglucagon in pancreatic alpha cells.1 In intestinal L-cells proglucagon is cleaved into glicentin, corresponding to proglucagon residues no 1-69. Glicentin can further be processed into oxyntomodulin, corresponding to proglucagon residues no 33-69. These peptides are released simultaneously upon stimulation.

Glucagon has shown to have an effect opposite to that of insulin, i.e. it raises blood glucose levels. It causes the liver to convert glycogen into glucose, which is then released into the blood stream.2-4 During hypoglycaemia, glucagon secretion offers a protective feedback mechanism, defending the organism against damaging effects of glucose deficiency in the brain and nerves.5

References:

1. Sandoval DA and D’Alessio DA. Physiology of Proglucagon Peptides: Role of Glucagon and GLP-1 in Health and Disease. Physiol Rev 95:513-548.
2. Bagger JI et al (2011) Glucagon antagonism as a potential therapeutic target in type 2 diabetes. Diabetes, Obesity and Metabolism 13:965-971.
3. Holst J et al (2004) Role of incretin hormones in the regulation of insulin secretion in diabetic and nondiabetic humans. Am J Physiol Endocrinol Metab 287: E199-206.
4. Holst J (2010) Glucagon and Glucagon-Like Peptides 1 and 2. Results Probl Cell Differ 50:121-135.
5. Young A (2005) Inhibition of Glucagon Secretion. Advances in Pharmacology 52:151-171.

Glucagon ELISA AL-157
D’Alessio D, Kumar A, Kalra B, Mistry S, Tong J. Novel ELISA Assays Demonstrate Specificity of Islet and Intestinal Processing of Proglucagon. Volume 4, Issue Supplement_1, April May 2020, SUN-LB124, https://doi.org/10

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Gray SM, Hoselton AL, Krishna R, Slentz CA, D’Alessio DA. GLP-1 Receptor Blockade Reduces Stimulated Insulin Secretion in Fasted Subjects With Low Circulating GLP-1. J Clin Endocrinol Metab. 2022 Aug 18;107(9):2500-2510. doi: 10.1210/clinem/dgac396. PMID: 35775723; PMCID: PMC9387711.

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Kim S, Abbasi F, Nachmanoff C, Kumar A, Kalra B, Savjani G, Mantzoros C. Effect of Liraglutide Treatment on Proglucagon-Derived Peptides. JESOCI, Volume 4, Abstract Supplement, 2020

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Kumar A, Kalra B, Mistry S, Patel AS, Budhavarapu V, Chatterji T, Savjani G, Krishna R, D’Alessio D. Development of Novel Specific and Sensitive ELISAs for Proglucagon-Derived Peptides. Poster presented at 69th AACC Meeting; 2017 July 30-Aug 3; San Diego, CA

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Perakakis N, Kalra B, Angelidi AM, Kumar A, Gavrieli A, MYannakoulia M, Mantzoros CS. Methods paper: Performance characteristics of novel assays for circulating levels of proglucagon-derived peptides and validation in a placebo controlled cross-over randomized clinical trial. Metabolism, Volume 129, 2022, 155157, ISSN 0026-0495, https://doi.org/10.1016/j.metabol.2022.155157.

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Polyzos SA, Perakakis N, Boutari C, Kountouras J, Ghaly W, Anastasilakis AD, Karagiannis A, Mantzoros CS. Targeted Analysis of Three Hormonal Systems Identifies Molecules Associated with the Presence and Severity of NAFLD. J Clin Endocrinol Metab. 2020 Mar 1;105(3):e390–400. doi: 10.1210/clinem/dgz172. PMID: 31690932; PMCID: PMC7112980.

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Shah A, Dodson WC, Kris-Etherton PM, Kunselman AR, Stetter CM, Gnatuk CL, Estes SJ, Allison KC, Sarwer DB, Sluss PM, Coutifaris C, Dokras A, Legro RS. Effects of Oral Contraception and Lifestyle Modification on Incretins and TGF-ß Superfamily Hormones in PCOS. J Clin Endocrinol Metab. 2021 Jan 1;106(1):108-119. doi: 10.1210/clinem/dgaa682. PMID: 32968804; PMCID: PMC7765645

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Stefanakis K, Kokkinos A, Argyrakopoulou G, et al. Circulating levels of proglucagon derived peptides are differentially regulated by the glucagon like peptide-1 agonist liraglutide and the centrally acting naltrexone/bupropion and can predict future weight loss and metabolic improvements: A 6-month long interventional study. Diabetes Obes Metab. 023;25(9):2561‐2574. doi:10.1111/dom.15141

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Upadhyay J, Panagiotou G, Anastasilakis A, Mantzoros C. Oxyntomodulin and Glucagon in Healthy Humans: Anthropometric, Hormonal, and Metabolic Predictors and Response to Glucose Load and Exercise. Abstract – ADA Supported Research, Integrated Physiology / Obesity. Not Dated

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Upadhyay J, Perakakis N, Panagiotou G, Anastasilakis AD, Mantzoros CS. Regulation of the proglucagon-derived hormones in healthy and in obese after bariatric surgery. Poster Presentation. Unknown Conference

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