Glucagon-like Peptide-1 Receptor Dependent Signaling in Cardiovascular Health and Disease: A Mini-review

Wu Q, Li D, Huang C, Zhang G, Wang Z, Liu J, et al. Glucose control independent mechanisms involved in the cardiovascular benefits of glucagon-like peptide-1 receptor agonists. Biomed Pharmacother. 2022;153:113517.

Article  CAS  PubMed  Google Scholar 

Helmstädter J, Keppeler K, Küster L, Münzel T, Daiber A, Steven S. Glucagon-like peptide-1 (GLP-1) receptor agonists and their cardiovascular benefits-the role of the GLP-1 receptor. Br J Pharmacol. 2022;179(4):659–76.

Article  PubMed  Google Scholar 

Guglielmi V, Sbraccia P. GLP-1 receptor independent pathways: emerging beneficial effects of GLP-1 breakdown products. Eat Weight Disord : EWD. 2017;22(2):231–40.

Article  PubMed  Google Scholar 

Ussher JR, Drucker DJ. Cardiovascular actions of incretin-based therapies. Circ Res. 2014;114(11):1788–803.

Article  CAS  PubMed  Google Scholar 

Winquist RJ, Gribkoff VK. Cardiovascular effects of GLP-1 receptor agonism. Adv Pharmacol. 2022;94:213–54.

Article  CAS  PubMed  Google Scholar 

Furness SGB, Christopoulos A, Sexton PM, Wootten D. Differential engagement of polar networks in the glucagon-like peptide 1 receptor by endogenous variants of the glucagon-like peptide 1. Biochem Pharmacol. 2018;156:223–40.

Article  CAS  PubMed  Google Scholar 

Huang Y, Wilkinson GF, Willars GB. Role of the signal peptide in the synthesis and processing of the glucagon-like peptide-1 receptor. Br J Pharmacol. 2010;159(1):237–51.

Article  CAS  PubMed  Google Scholar 

Liu T, Naidoo NR, Agyemang E, Lamichhane R. Insights into the structural dynamics of the secretin family (class B1) G protein-coupled receptors. J Biol Chem. 2025;301(8):110466.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Liang YL, Khoshouei M, Radjainia M, Zhang Y, Glukhova A, Tarrasch J, et al. Phase-plate cryo-EM structure of a class B GPCR-G-protein complex. Nature. 2017;546(7656):118–23.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Wan W, Qin Q, Xie L, Zhang H, Wu F, Stevens RC, et al. GLP-1R signaling and functional molecules in incretin therapy. Molecules. 2023. https://doi.org/10.3390/molecules28020751.

Article  PubMed  PubMed Central  Google Scholar 

Marzook A, Tomas A, Jones B. The interplay of glucagon-like peptide-1 receptor trafficking and signalling in pancreatic beta cells. Front Endocrinol (Lausanne). 2021;12:678055.

Article  PubMed  PubMed Central  Google Scholar 

Modvig IM, Smits MM, Galsgaard KD, Hjørne AP, Drzazga AK, Rosenkilde MM, et al. L-valine is a powerful stimulator of GLP-1 secretion in rodents and stimulates secretion through ATP-sensitive potassium channels and voltage-gated calcium channels. Nutr Diabetes. 2024;14(1):43.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Yang Y, Yamane S, Harada N, Ikeguchi-Ogura E, Yamamoto K, Wada N, et al. Voltage-gated calcium channel α2δ-1 subunit is involved in the regulation of glucose-stimulated GLP-1 secretion in mice. Am J Physiol Gastrointest Liver Physiol. 2025;328(3):G243–51.

Article  CAS  PubMed  Google Scholar 

Lymperopoulos A, Borges JI, Stoicovy RA. Cyclic adenosine monophosphate in cardiac and sympathoadrenal GLP-1 receptor signaling: focus on anti-inflammatory effects. Pharmaceutics. 2024;16(6):693.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Borah MP, Trakroo D, Soni N, Kumari P, Baidya M. Exploring bias in GPCR signaling and its implication in drug development: a one-sided affair. Biochemistry. 2025;64(1):1–14.

Article  CAS  PubMed  Google Scholar 

Plouffe B, Thomsen ARB, Irannejad R. Emerging role of compartmentalized G protein-coupled receptor signaling in the cardiovascular field. ACS Pharmacol Transl Sci. 2020;3(2):221–36.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Talbot J, Joly E, Prentki M, Buteau J. β-Arrestin1-mediated recruitment of c-Src underlies the proliferative action of glucagon-like peptide-1 in pancreatic β INS832/13 cells. Mol Cell Endocrinol. 2012;364(1–2):65–70.

Article  CAS  PubMed  Google Scholar 

Quoyer J, Longuet C, Broca C, Linck N, Costes S, Varin E, et al. GLP-1 mediates antiapoptotic effect by phosphorylating Bad through a beta-arrestin 1-mediated ERK1/2 activation in pancreatic beta-cells. J Biol Chem. 2010;285(3):1989–2002.

Article  CAS  PubMed  Google Scholar 

Taguchi K, Kaneko N, Okudaira K, Matsumoto T, Kobayashi T. GLP-1 modulates insulin-induced relaxation response through β-arrestin2 regulation in diabetic mice aortas. Acta Physiol (Oxf). 2021;231(3):e13573.

Article  CAS  PubMed  Google Scholar 

Baggio LL, Yusta B, Mulvihill EE, Cao X, Streutker CJ, Butany J, et al. GLP-1 Receptor Expression Within the Human Heart. Endocrinology. 2018;159(4):1570–84.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Clarke SJ, Giblett JP, Yang LL, Hubsch A, Zhao T, Aetesam-Ur-Rahman M, et al. GLP-1 is a coronary artery vasodilator in humans. J Am Heart Assoc. 2018;7(22):e010321.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ban K, Noyan-Ashraf MH, Hoefer J, Bolz SS, Drucker DJ, Husain M. Cardioprotective and vasodilatory actions of glucagon-like peptide 1 receptor are mediated through both glucagon-like peptide 1 receptor-dependent and -independent pathways. Circulation. 2008;117(18):2340–50.

Article  CAS  PubMed  Google Scholar 

Pyke C, Heller RS, Kirk RK, Ørskov C, Reedtz-Runge S, Kaastrup P, et al. GLP-1 receptor localization in monkey and human tissue: novel distribution revealed with extensively validated monoclonal antibody. Endocrinology. 2014;155(4):1280–90.

Article  PubMed  Google Scholar 

Siraj MA, Mundil D, Beca S, Momen A, Shikatani EA, Afroze T, et al. Cardioprotective GLP-1 metabolite prevents ischemic cardiac injury by inhibiting mitochondrial trifunctional protein-α. J Clin Invest. 2020;130(3):1392–404.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ying W, Meiyan S, Wen C, Kaizu X, Meifang W, Liming L. Liraglutide ameliorates oxidized LDL-induced endothelial dysfunction by GLP-1R-dependent downregulation of LOX-1-mediated oxidative stress and inflammation. Redox Rep. 2023;28(1):2218684.

Article  PubMed  PubMed Central  Google Scholar 

Baek CH, Kim H, Moon SY, Yang WS. Liraglutide, a glucagon-like peptide-1 receptor agonist, induces ADAM10-dependent ectodomain shedding of RAGE via AMPK activation in human aortic endothelial cells. Life Sci. 2022;292:120331.

Article  CAS  PubMed  Google Scholar 

Richards P, Parker HE, Adriaenssens AE, Hodgson JM, Cork SC, Trapp S, et al. Identification and characterization of GLP-1 receptor-expressing cells using a new transgenic mouse model. Diabetes. 2014;63(4):1224–33.

Article  CAS  PubMed  Google Scholar 

Kimura T, Obata A, Shimoda M, Okauchi S, Hirukawa H, Kohara K, et al. Decreased glucagon-like peptide 1 receptor expression in endothelial and smooth muscle cells in diabetic db/db mice: TCF7L2 is a possible regulator of the vascular glucagon-like peptide 1 receptor. Diab Vasc Dis Res. 2017;14(6):540–8.

Article  CAS  PubMed  Google Scholar 

Körner M, Stöckli M, Waser B, Reubi JC. GLP-1 receptor expression in human tumors and human normal tissues: potential for in vivo targeting. J Nucl Med. 2007;48(5):736–43.

Article  PubMed  Google Scholar 

Twarda-Clapa A, Olczak A, Białkowska AM, Koziołkiewicz M. Advanced glycation end-products (AGEs): formation, chemistry, classification, receptors, and diseas

Comments (0)

No login
gif