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Synthesis and anti‐diabetic activity of novel biphenylsulfonamides as glucagon receptor antagonists
Type 2 diabetes is characterized by chronic hyperglycemia. Insulin, a hormone secreted from pancreatic β‐cells, decreases blood glucose levels, and glucagon, a hormone secreted from pancreatic α‐cells, increases blood glucose levels by counterregulation of insulin through stimulation of hepatic gluc...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9291748/ https://www.ncbi.nlm.nih.gov/pubmed/34310065 http://dx.doi.org/10.1111/cbdd.13928 |
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author | Lee, Chang‐Yong Choi, Hojung Park, Eun‐Young Nguyen, Thi‐Thao‐Linh Maeng, Han‐Joo Mee Lee, Kyoung Jun, Hee‐Sook Shin, Dongyun |
author_facet | Lee, Chang‐Yong Choi, Hojung Park, Eun‐Young Nguyen, Thi‐Thao‐Linh Maeng, Han‐Joo Mee Lee, Kyoung Jun, Hee‐Sook Shin, Dongyun |
author_sort | Lee, Chang‐Yong |
collection | PubMed |
description | Type 2 diabetes is characterized by chronic hyperglycemia. Insulin, a hormone secreted from pancreatic β‐cells, decreases blood glucose levels, and glucagon, a hormone secreted from pancreatic α‐cells, increases blood glucose levels by counterregulation of insulin through stimulation of hepatic glucose production. In diabetic patients, dysregulation of glucagon secretion contributes to hyperglycemia. Thus, inhibition of the glucagon receptor is one strategy for the treatment of hyperglycemia in type 2 diabetes. In this paper, we report a series of biphenylsulfonamide derivatives that were designed, synthesized, and then evaluated by cAMP and hepatic glucose production assays as glucagon receptor antagonists. Of these, compound 7aB‐3 decreased glucagon‐induced cAMP production and glucagon‐induced glucose production in the in vitro assays. Glucagon challenge tests and glucose tolerance tests showed that compound 7aB‐3 significantly inhibited glucagon‐induced glucose increases and improved glucose tolerance. These results suggest that compound 7aB‐3 has therapeutic potential for the treatment of type 2 diabetes. |
format | Online Article Text |
id | pubmed-9291748 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-92917482022-07-20 Synthesis and anti‐diabetic activity of novel biphenylsulfonamides as glucagon receptor antagonists Lee, Chang‐Yong Choi, Hojung Park, Eun‐Young Nguyen, Thi‐Thao‐Linh Maeng, Han‐Joo Mee Lee, Kyoung Jun, Hee‐Sook Shin, Dongyun Chem Biol Drug Des Research Articles Type 2 diabetes is characterized by chronic hyperglycemia. Insulin, a hormone secreted from pancreatic β‐cells, decreases blood glucose levels, and glucagon, a hormone secreted from pancreatic α‐cells, increases blood glucose levels by counterregulation of insulin through stimulation of hepatic glucose production. In diabetic patients, dysregulation of glucagon secretion contributes to hyperglycemia. Thus, inhibition of the glucagon receptor is one strategy for the treatment of hyperglycemia in type 2 diabetes. In this paper, we report a series of biphenylsulfonamide derivatives that were designed, synthesized, and then evaluated by cAMP and hepatic glucose production assays as glucagon receptor antagonists. Of these, compound 7aB‐3 decreased glucagon‐induced cAMP production and glucagon‐induced glucose production in the in vitro assays. Glucagon challenge tests and glucose tolerance tests showed that compound 7aB‐3 significantly inhibited glucagon‐induced glucose increases and improved glucose tolerance. These results suggest that compound 7aB‐3 has therapeutic potential for the treatment of type 2 diabetes. John Wiley and Sons Inc. 2021-08-01 2021-11 /pmc/articles/PMC9291748/ /pubmed/34310065 http://dx.doi.org/10.1111/cbdd.13928 Text en © 2021 The Authors. Chemical Biology & Drug Design published by John Wiley & Sons Ltd. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Research Articles Lee, Chang‐Yong Choi, Hojung Park, Eun‐Young Nguyen, Thi‐Thao‐Linh Maeng, Han‐Joo Mee Lee, Kyoung Jun, Hee‐Sook Shin, Dongyun Synthesis and anti‐diabetic activity of novel biphenylsulfonamides as glucagon receptor antagonists |
title | Synthesis and anti‐diabetic activity of novel biphenylsulfonamides as glucagon receptor antagonists |
title_full | Synthesis and anti‐diabetic activity of novel biphenylsulfonamides as glucagon receptor antagonists |
title_fullStr | Synthesis and anti‐diabetic activity of novel biphenylsulfonamides as glucagon receptor antagonists |
title_full_unstemmed | Synthesis and anti‐diabetic activity of novel biphenylsulfonamides as glucagon receptor antagonists |
title_short | Synthesis and anti‐diabetic activity of novel biphenylsulfonamides as glucagon receptor antagonists |
title_sort | synthesis and anti‐diabetic activity of novel biphenylsulfonamides as glucagon receptor antagonists |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9291748/ https://www.ncbi.nlm.nih.gov/pubmed/34310065 http://dx.doi.org/10.1111/cbdd.13928 |
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