دورية أكاديمية
Novel glucagon-like peptide-1 analogue exhibits potency-driven G-protein biased agonism with promising effects on diabetes and diabetic dry eye syndrome
| العنوان: | Novel glucagon-like peptide-1 analogue exhibits potency-driven G-protein biased agonism with promising effects on diabetes and diabetic dry eye syndrome |
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| المؤلفون: | Yongna Hao, Min Wei, Ning Zhang, Xinying Zhang |
| المصدر: | Bioengineered, Vol 13, Iss 3, Pp 5467-5479 (2022) |
| بيانات النشر: | Taylor & Francis Group |
| سنة النشر: | 2022 |
| المجموعة: | Directory of Open Access Journals: DOAJ Articles |
| مصطلحات موضوعية: | glp-1, g-protein, long-lasting diabetes, dry eye syndrome, obesity, Biotechnology, TP248.13-248.65 |
| الوصف: | Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are considered as effective treatments for type 2 diabetes. Here, we describe the in vitro characteristics and in vivo anti-diabetic efficacies of a novel GLP-1RA, termed SM102. The in vitro functions of SM102, including GLP-1R kinetic binding parameter, cAMP activation, endocytosis and recycling, were all evaluated using the INS-1 832/13 cells expressing human GLP-1R. Chronic efficacies study was performed to evaluate the effects of SM102 on the glycemic benefits, body weight loss and other diabetic complications in db/db mice. As a result, SM102 exhibited enhanced binding affinity and potency-driven bias in favor of cAMP over GLP-1R endocytosis and β-Arrestin 2 recruitment, as well as comparable insulin secretory response compared with Semaglutide. In addition, chronic treatment of SM102 led to more promising therapeutical effects on hyperglycemia, weight control and insulin resistance as well as dry eye syndrome (DES) than Semaglutide. Furthermore, SM102 could ameliorate diabetic DES via improving antioxidant properties, inflammatory factors and inhibiting MAPKs pathway in diabetic mice. In conclusion, SM102 is a G protein-biased agonist serving as a promising new GLP-1RA for treating diabetes and diabetic complications. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 2165-5979 2165-5987 |
| العلاقة: | http://dx.doi.org/10.1080/21655979.2022.2031418Test; https://doaj.org/toc/2165-5979Test; https://doaj.org/toc/2165-5987Test; https://doaj.org/article/6c2848e20fd144159ea2344c68d0934bTest |
| DOI: | 10.1080/21655979.2022.2031418 |
| الإتاحة: | https://doi.org/10.1080/21655979.2022.2031418Test https://doaj.org/article/6c2848e20fd144159ea2344c68d0934bTest |
| رقم الانضمام: | edsbas.8A40B459 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 21655979 21655987 |
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| DOI: | 10.1080/21655979.2022.2031418 |