Glucagon-Like Peptide-2 (GLP-2) is a 33-amino acid gut hormone produced by the intestinal L-cells and various neurons in the central nervous system1-3. Posttranslational proteolytic cleavage of proglucagon molecule produces GLP-2 along with GLP-1. Intestinal GLP-2 is co-secreted along with GLP-1 upon nutrient ingestion. GLP-2 is released in response to stimulation by luminal nutrients, such as glucose, fatty acids and dietary fiber4. GLP-2 is cleaved by proteolytic enzymes into active form (1-33) and inactive form (3-33). The GLP-2 sequence is highly conserved among mammals and is involved in regulating gut mucosal growth and integrity. The main biological actions of GLP-2 are related to the regulation of energy absorption and maintenance of mucosal morphology, function and integrity of the intestine; however, recent experimental animal studies suggested that GLP-2 exerts beneficial effects on glucose metabolism in conditions related to increased uptake of energy, such as obesity. GLP-2 acts in an endocrine fashion to link intestinal growth and metabolism with nutrient intake4. GLP-2 acts as a beneficial factor for glucose metabolism in mice with high-fat diet-induced obesity5. GLP-2 and related analogs may be used as therapeutics for short bowel syndrome, Crohn’s disease, osteoporosis and as adjuvant therapy during cancer chemotherapy. Measuring plasma levels of GLP-2 in research, preclinical and clinical studies of Type 2 Diabetes and obesity will open new avenue for diagnostics and therapeutics.

References:
1. Müller et al., (2017) The New Biology and Pharmacology of Glucagon. Physiol Rev 97: 721–766.
2. Drucker DJ, Habener JF, Holst JJ Discovery, characterization, and clinical development of the glucagon-like peptides (2017) J Clin Invest. 127(12):4217-4227.
3. Vrang N, Hansen M, Larsen PJ & Tang-Christensen M 2007 Characterization of brainstem preproglucagon projections to the paraventricular and dorsomedial hypothalamic nuclei. Brain Research 1149 118–126
4. Amato A, Baldassano and Flavia Mulè. GLP2: an underestimated signal for improving glycaemic control and insulin sensitivity. Journal of Endocrinology (2016) 229, R57–R66
5. Baldassano S, Amato A, Rappa F, Cappello F & Mulè F (2016b) Influence of endogenous glucagon like peptide-2 on lipid disorders in mice fed a high fat diet. Endocrine Research.
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6. HHS Publication, 5th ed., 2007. Biosafety in Microbiological and Biomedical Laboratories. Available http://www.cdc.gov/biosafety/publications/bmbl5/BMBL5
7. DHHS (NIOSH) Publication No. 78–127, August 1976. Current Intelligence Bulletin 13 – Explosive Azide Hazard. Available: http:// www.cdc.gov/niosh.
8. Kricka L. Interferences in immunoassays – still a threat. Clin Chem 2000; 46: 1037–1038.

GLP-2 ELISA AL-174
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

All Products Cited: GLP-1 ELISA AL-172; GLP-2 ELISA AL-174; Glucagon ELISA AL-157; Oxyntomodulin ELISA AL-139; Glicentin ELISA AL-185; MPGF ELISA AL-175

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.

All Products Cited: GLP-1 ELISA AL-172; GLP-2 ELISA AL-174; Oxyntomodulin ELISA AL-139; Glicentin ELISA AL-185; Glucagon ELISA AL-157; MPGF ELISA AL-175; C-Peptide of Insulin ELISA AL-151

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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