Oral administration of l-lysine potently promotes GLP-1 secretion and lowers glycemic response in rats

Glucagon-like peptide-1 (GLP-1) is a gastrointestinal hormone that suppresses postprandial glycemia and appetite. GLP-1 secretion is promoted by various nutrients; however, studies on the effects of orally administered amino acids on GLP-1 secretion are limited. This study investigated the acute effects of l-lysine (Lys) on GLP-1 secretion in vivo and explored the underlying mechanisms. In male Sprague-Dawley rats, oral administration Lys, but not l-Alanine (Ala), elevated plasma GLP-1 concentrations, with comparable to or higher potency compared to other amino acids known to stimulate GLP-1 secretion. Duodenal administration of CaSR antagonist attenuated Lys-induced GLP-1 secretion. Oral co-administration of Lys and calcium potently promoted GLP-1 secretion and lowered glycemia under an oral glucose tolerance test. These findings demonstrate that Lys potently induces GLP-1 secretion in vivo, and the combination of Lys and calcium has translational potential as potent GLP-1 releasing strategy for the management of blood glucose levels.