AMG 837: a novel GPR40/FFA1 agonist that enhances insulin secretion and lowers glucose levels in rodents.
Agonists of GPR40 (FFA1) have been proposed as a means to treat type 2 diabetes. Through lead optimization of a high throughput screening hit, we have identified a novel GPR40 agonist called AMG 837. The objective of these studies was to understand the preclinical pharmacological properties of AMG 8...
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2011
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oai:doaj.org-article:729ea24e76304c709713d2c9927fb9032021-11-18T07:34:45ZAMG 837: a novel GPR40/FFA1 agonist that enhances insulin secretion and lowers glucose levels in rodents.1932-620310.1371/journal.pone.0027270https://doaj.org/article/729ea24e76304c709713d2c9927fb9032011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22087278/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Agonists of GPR40 (FFA1) have been proposed as a means to treat type 2 diabetes. Through lead optimization of a high throughput screening hit, we have identified a novel GPR40 agonist called AMG 837. The objective of these studies was to understand the preclinical pharmacological properties of AMG 837. The activity of AMG 837 on GPR40 was characterized through GTPγS binding, inositol phosphate accumulation and Ca(2+) flux assays. Activity of AMG 837 on insulin release was assessed on isolated primary mouse islets. To determine the anti-diabetic activity of AMG 837 in vivo, we tested AMG 837 using a glucose tolerance test in normal Sprague-Dawley rats and obese Zucker fatty rats. AMG 837 was a potent partial agonist in the calcium flux assay on the GPR40 receptor and potentiated glucose stimulated insulin secretion in vitro and in vivo. Acute administration of AMG 837 lowered glucose excursions and increased glucose stimulated insulin secretion during glucose tolerance tests in both normal and Zucker fatty rats. The improvement in glucose excursions persisted following daily dosing of AMG 837 for 21-days in Zucker fatty rats. Preclinical studies demonstrated that AMG 837 was a potent GPR40 partial agonist which lowered post-prandial glucose levels. These studies support the potential utility of AMG 837 for the treatment of type 2 diabetes.Daniel C-H LinJane ZhangRun ZhuangFrank LiKathy NguyenMichael ChenThanhvien TranEdwin LopezJenny Ying Lin LuXiaoyan Nina LiLiang TangGeorge R TonnGayathri SwaminathJeff D ReaganJin-Long ChenHui TianYi-Jyun LinJonathan B HouzeJian LuoPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 11, p e27270 (2011) |
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DOAJ |
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| topic |
Medicine R Science Q |
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Medicine R Science Q Daniel C-H Lin Jane Zhang Run Zhuang Frank Li Kathy Nguyen Michael Chen Thanhvien Tran Edwin Lopez Jenny Ying Lin Lu Xiaoyan Nina Li Liang Tang George R Tonn Gayathri Swaminath Jeff D Reagan Jin-Long Chen Hui Tian Yi-Jyun Lin Jonathan B Houze Jian Luo AMG 837: a novel GPR40/FFA1 agonist that enhances insulin secretion and lowers glucose levels in rodents. |
| description |
Agonists of GPR40 (FFA1) have been proposed as a means to treat type 2 diabetes. Through lead optimization of a high throughput screening hit, we have identified a novel GPR40 agonist called AMG 837. The objective of these studies was to understand the preclinical pharmacological properties of AMG 837. The activity of AMG 837 on GPR40 was characterized through GTPγS binding, inositol phosphate accumulation and Ca(2+) flux assays. Activity of AMG 837 on insulin release was assessed on isolated primary mouse islets. To determine the anti-diabetic activity of AMG 837 in vivo, we tested AMG 837 using a glucose tolerance test in normal Sprague-Dawley rats and obese Zucker fatty rats. AMG 837 was a potent partial agonist in the calcium flux assay on the GPR40 receptor and potentiated glucose stimulated insulin secretion in vitro and in vivo. Acute administration of AMG 837 lowered glucose excursions and increased glucose stimulated insulin secretion during glucose tolerance tests in both normal and Zucker fatty rats. The improvement in glucose excursions persisted following daily dosing of AMG 837 for 21-days in Zucker fatty rats. Preclinical studies demonstrated that AMG 837 was a potent GPR40 partial agonist which lowered post-prandial glucose levels. These studies support the potential utility of AMG 837 for the treatment of type 2 diabetes. |
| format |
article |
| author |
Daniel C-H Lin Jane Zhang Run Zhuang Frank Li Kathy Nguyen Michael Chen Thanhvien Tran Edwin Lopez Jenny Ying Lin Lu Xiaoyan Nina Li Liang Tang George R Tonn Gayathri Swaminath Jeff D Reagan Jin-Long Chen Hui Tian Yi-Jyun Lin Jonathan B Houze Jian Luo |
| author_facet |
Daniel C-H Lin Jane Zhang Run Zhuang Frank Li Kathy Nguyen Michael Chen Thanhvien Tran Edwin Lopez Jenny Ying Lin Lu Xiaoyan Nina Li Liang Tang George R Tonn Gayathri Swaminath Jeff D Reagan Jin-Long Chen Hui Tian Yi-Jyun Lin Jonathan B Houze Jian Luo |
| author_sort |
Daniel C-H Lin |
| title |
AMG 837: a novel GPR40/FFA1 agonist that enhances insulin secretion and lowers glucose levels in rodents. |
| title_short |
AMG 837: a novel GPR40/FFA1 agonist that enhances insulin secretion and lowers glucose levels in rodents. |
| title_full |
AMG 837: a novel GPR40/FFA1 agonist that enhances insulin secretion and lowers glucose levels in rodents. |
| title_fullStr |
AMG 837: a novel GPR40/FFA1 agonist that enhances insulin secretion and lowers glucose levels in rodents. |
| title_full_unstemmed |
AMG 837: a novel GPR40/FFA1 agonist that enhances insulin secretion and lowers glucose levels in rodents. |
| title_sort |
amg 837: a novel gpr40/ffa1 agonist that enhances insulin secretion and lowers glucose levels in rodents. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2011 |
| url |
https://doaj.org/article/729ea24e76304c709713d2c9927fb903 |
| work_keys_str_mv |
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