The signalling association of glucagon-like peptide-1 and its receptors in the gastrointestinal tract and GPR40 and insulin receptor in the pancreas of sheep

Sep 3, 2024General and comparative endocrinology

Signaling links of glucagon-like peptide-1 and its receptors in the sheep gut and GPR40 with insulin receptor in the pancreas

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Abstract

Postprandial GLP-1 and insulin increased by 3.7-4.1 and 1.45-1.5 times, respectively, in sheep supplemented with calcium salts of long-chain fatty acids.

Supplementation with calcium salts of long-chain fatty acids (CSFAs) is associated with increased GLP-1 and insulin levels.
Glucagon and glucose levels decreased post-feeding in sheep supplemented with CSFAs compared to those without.
The expression of GLP-1 receptor in the gastrointestinal tract and pancreas increased with CSFA supplementation.
G-protein-coupled receptor 40 in the pancreas is involved in sensing long-chain fatty acids and triggering signaling pathways.
Increased GLP-1 and GLP-1 receptor levels may lead to moderately increased insulin secretion and lower glucagon levels.

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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.

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The signalling association of glucagon-like peptide-1 and its receptors in the gastrointestinal tract and GPR40 and insulin receptor in the pancreas of sheep

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