Animal Physiology Division, ICAR-National Institute of Animal Nutrition and Physiology, Bangalore 560030, India.
Animal Nutrition Division, ICAR-National Institute of Animal Nutrition and Physiology, Bangalore 560030, India.
Gen Comp Endocrinol. 2024 Nov 1;358:114602. doi: 10.1016/j.ygcen.2024.114602. Epub 2024 Sep 1.
The present study was aimed at gaining insight into the signalling relationship between glucagon-like peptide-1 (GLP-1) and its receptor (GLP-1R) in the regulation of glucose metabolism. Further, to assess the role of G-protein-coupled receptor 40 (GPR40) and insulin receptor (INSR) in the pancreas of sheep that were supplemented with calcium salts of long-chain fatty acids (CSFAs). An experiment was carried out over a period of 60 days with eighteen sheep, and they were fed with a standard basal diet. The sheep were divided into three groups: CSFA0 (without CSFAs), while CSFA3 and CSFA5 were supplemented with 3 % and 5 % of CSFAs, respectively. Plasma concentrations of GLP-1, insulin, glucagon, and glucose were assessed every two weeks. At the end of the experiment, sheep were slaughtered, and samples of gastrointestinal tract (GIT) epithelial tissues and pancreas were collected to assess the relative expression of mRNA of GPR40, GLP-1R, and INSR. Postprandial GLP-1 and insulin were increased by 3.7-4.1 and 1.45-1.5 times, respectively, in the CSFAs-supplemented groups compared to CSFA0. Post-feeding, glucagon and glucose levels decreased in CSFA3 and CSFA5 compared to CSFA0. The results indicated that the supplementation of LCFAs increased the expression of GLP-1R in the GIT and pancreas, as well as the mRNA of GPR40 and INSR in the pancreas. Chemosensing of LCFAs by GPR40 in the pancreas triggers signalling transduction, and enhanced GLP-1 and GLP-1R resulted in moderately increased insulin secretion and reduced glucagon levels. These combined effects, along with the glucose-lowering effect of GLP-1, effectively lowered glucose levels in normoglycemic sheep.
本研究旨在深入了解胰高血糖素样肽-1（GLP-1）与其受体（GLP-1R）在葡萄糖代谢调节中的信号关系。此外，评估长链脂肪酸钙盐（CSFAs）补充后绵羊胰腺中 G 蛋白偶联受体 40（GPR40）和胰岛素受体（INSR）的作用。该实验在 60 天内对 18 只绵羊进行，它们喂食标准基础日粮。绵羊分为三组：CSFA0（无 CSFAs），CSFA3 和 CSFA5 分别补充 3%和 5%的 CSFAs。每两周评估一次 GLP-1、胰岛素、胰高血糖素和血糖的血浆浓度。实验结束时，宰杀绵羊，采集胃肠道（GIT）上皮组织和胰腺样本，评估 GPR40、GLP-1R 和 INSR 的相对 mRNA 表达。与 CSFA0 相比，CSFA 补充组餐后 GLP-1 和胰岛素分别增加了 3.7-4.1 倍和 1.45-1.5 倍。CSFA3 和 CSFA5 组餐后胰高血糖素和葡萄糖水平较 CSFA0 组降低。结果表明，LCFAs 的补充增加了 GIT 和胰腺中 GLP-1R 的表达，以及胰腺中 GPR40 和 INSR 的 mRNA 表达。GPR40 对 LCFAs 的化学感应触发信号转导，增强的 GLP-1 和 GLP-1R 导致胰岛素分泌适度增加和胰高血糖素水平降低。这些综合作用，加上 GLP-1 的降血糖作用，有效降低了正常血糖绵羊的血糖水平。
