The therapeutic potential of GLP‐1 receptor biased agonism
| العنوان: | The therapeutic potential of GLP‐1 receptor biased agonism |
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| المؤلفون: | Ben Jones |
| المساهمون: | Imperial College Healthcare NHS Trust- BRC Funding, Medical Research Council (MRC), The Academy of Medical Sciences, Society for Endocrinology, European Foundation for the Study of Diabetes, British Society for Neuroendocrinology |
| المصدر: | British Journal of Pharmacology. 179:492-510 |
| بيانات النشر: | Wiley, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 0301 basic medicine, endocrine system, Side effect, medicine.medical_treatment, Pharmacology, Glucagon-Like Peptide-1 Receptor, 03 medical and health sciences, 0302 clinical medicine, Downregulation and upregulation, Glucagon-Like Peptide 1, medicine, Functional selectivity, Animals, Insulin, insulin release, Pharmacology & Pharmacy, Receptor, Glucagon-like peptide 1 receptor, β-arrestin, business.industry, Nausea, 030104 developmental biology, biased agonism, Diabetes Mellitus, Type 2, appetite regulation, Animal studies, 1115 Pharmacology and Pharmaceutical Sciences, business, 030217 neurology & neurosurgery, Intracellular |
| الوصف: | Glucagon-like peptide-1 (GLP-1) receptor agonists are effective treatments for type 2 diabetes as they stimulate insulin release and promote weight loss through appetite suppression. Their main side effect is nausea. All approved GLP-1 agonists are full agonists across multiple signalling pathways. However, selective engagement with specific intracellular effectors, or biased agonism, has been touted as a means to improve GLP-1 agonists therapeutic efficacy. In this review, I critically examine how GLP-1 receptor-mediated intracellular signalling is linked to physiological responses and discuss the implications of recent studies investigating the metabolic effects of biased GLP-1 agonists. Overall, there is little conclusive evidence that beneficial and adverse effects of GLP-1 agonists are attributable to distinct, nonoverlapping signalling pathways. Instead, G protein-biased GLP-1 agonists appear to achieve enhanced anti-hyperglycaemic efficacy by avoiding GLP-1 receptor desensitisation and downregulation, partly via reduced β-arrestin recruitment. This effect seemingly applies more to insulin release than to appetite regulation and nausea, possible reasons for which are discussed. At present, most evidence derives from cellular and animal studies, and more human data are required to determine whether this approach represents a genuine therapeutic advance. LINKED ARTICLES: This article is part of a themed issue on GLP1 receptor ligands (BJP 75th Anniversary). To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.4/issuetocTest. |
| تدمد: | 1476-5381 0007-1188 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::afdfdafdc98b03ee51d74bcad2324cd4Test https://doi.org/10.1111/bph.15497Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....afdfdafdc98b03ee51d74bcad2324cd4 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14765381 00071188 |
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