Long-chain fatty acids are ligands of G-protein-coupled receptor (GPR) 40 and GPR120 as well as a major nutrient in dietary fat. Pretreatment with GPR40 agonists enhanced the secretion of insulin in response to elevating blood glucose levels, but pretreatment with GPR120 agonist did not ameliorate postprandial hyperglycemia. This study examined whether oral administration of linoleic acid (LA), a GPR40 and GPR120 agonist, immediately before glucose load would affect the elevation of postprandial blood glucose levels in rats.
The elevation of postprandial blood glucose levels was slowed by LA but not by trilinolein in rats without promotion of insulin secretion, and the effect was also observed in rats with type 1 diabetes. However, LA did not inhibit the sodium-dependent glucose transporter 1 transport in CACO-2 cells. LA slowed the gastric emptying 15 min after glucose load, and glucagon-like peptide 1 (GLP-1), but not cholecystokinin, level was elevated by LA 15 min after glucose load. GPR120 agonist ameliorated postprandial hyperglycemia but GPR40 agonist did not. Pretreatment with a GPR120 antagonist, partially canceled the improvement of postprandial hyperglycemia induced by LA.
Oral administration of LA immediately after glucose load ameliorated postprandial hyperglycemia due to slowing of gastric emptying via promotion of GLP-1 secretion. The mechanisms may be associated with GPR120 pathway.