Discovery of a novel oxime ether scaffold as potent and orally bioavailable free fatty acid receptor 1 agonists

RSC Advances ◽  
2016 ◽  
Vol 6 (52) ◽  
pp. 46356-46365 ◽  
Author(s):  
Zheng Li ◽  
Jianyong Yang ◽  
Weijie Gu ◽  
Guoshen Cao ◽  
Xiaoting Fu ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Fatty Acid ◽  
Free Fatty Acid ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Acid Receptor ◽  
Free Fatty Acid Receptor ◽  
Orally Bioavailable ◽  
Glucose Stimulated Insulin Secretion ◽  
Fatty Acid Receptor

The free fatty acid receptor 1 (FFA1) plays a key role in amplifying glucose-stimulated insulin secretion in pancreatic β-cells.

scholarly journals PPAR-γ Activation Increases Insulin Secretion through the Up-regulation of the Free Fatty Acid Receptor GPR40 in Pancreatic β-Cells

PLoS ONE ◽  
2013 ◽  
Vol 8 (1) ◽  
pp. e50128 ◽  
Author(s):  
Hyo-Sup Kim ◽  
You-Cheol Hwang ◽  
Seung-Hoi Koo ◽  
Kyong Soo Park ◽  
Myung-Shik Lee ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Fatty Acid ◽  
Free Fatty Acid ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Acid Receptor ◽  
Ppar Γ ◽  
Free Fatty Acid Receptor ◽  
Fatty Acid Receptor

scholarly journals Free fatty acid receptor 3 differentially contributes to β-cell compensation under high-fat diet and streptozotocin stress

2020 ◽  
Vol 318 (4) ◽  
pp. R691-R700 ◽  
Author(s):  
Medha Priyadarshini ◽  
Connor Cole ◽  
Gautham Oroskar ◽  
Anton E. Ludvik ◽  
Barton Wicksteed ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Fatty Acid ◽  
Free Fatty Acid ◽  
Cell Mass ◽  
Insulin Response ◽  
High Fat ◽  
Β Cell ◽  
Acid Receptor ◽  
Free Fatty Acid Receptor ◽  
Fatty Acid Receptor

The free fatty acid receptor 3 (FFA3) is a nutrient sensor of gut microbiota-generated nutrients, the short-chain fatty acids. Previously, we have shown that FFA3 is expressed in β-cells and inhibits islet insulin secretion ex vivo. Here, we determined the physiological relevance of the above observation by challenging wild-type (WT) and FFA3 knockout (KO) male mice with 1) hyperglycemia and monitoring insulin response via highly sensitive hyperglycemic clamps, 2) dietary high fat (HF), and 3) chemical-induced diabetes. As expected, FFA3 KO mice exhibited significantly higher insulin secretion and glucose infusion rate in hyperglycemic clamps. Predictably, under metabolic stress induced by HF-diet feeding, FFA3 KO mice exhibited less glucose intolerance compared with the WT mice. Moreover, similar islet architecture and β-cell area in HF diet-fed FFA3 KO and WT mice was observed. Upon challenge with streptozotocin (STZ), FFA3 KO mice initially exhibited a tendency for an accelerated incidence of diabetes compared with the WT mice. However, this difference was not maintained. Similar glycemia and β-cell mass loss was observed in both genotypes 10 days post-STZ challenge. Higher resistance to STZ-induced diabetes in WT mice could be due to higher basal islet autophagy. However, this difference was not protective because in response to STZ, similar autophagy induction was observed in both WT and FFA3 KO islets. These data demonstrate that FFA3 plays a role in modulating insulin secretion and β-cell response to stressors. The β-cell FFA3 and autophagy link warrant further research.

Sign in / Sign up

Export Citation Format

Share Document