OBJECTIVE: Oxytocin (Oxt) is secreted to the peripheral body through the pituitary gland and can induce insulin secretion under high glucose conditions. Insulin secretion is regulated by various factors including glucagon-like peptide (GLP)-1, secreted from intestinal L-cells. GLP-1 is also expressed and secreted within islets and termed as "intra-islet GLP-1". The study aims to elucidate the impact of Oxt on insulin secretion in relation to intra-islet GLP-1. METHODS: We measured changes in blood glucose and insulin levels following Oxt administration in wild-type (WT) and Oxt receptor knockout (OxtR KO) mice. Additionally, we assessed insulin secretion from islets isolated from WT and OxtR KO mice under conditions with and without Oxt. Histological analysis of OxtR expression in islets was performed. The effects of Oxt on factors influencing insulin secretion, such as glucagon, GLP-1 secretion from WT islets and K(ATP) channel activity were also investigated. RESULTS: Oxt injection induced a temporal rise in blood glucose levels in both WT and OxtR-KO mice at 15-min post-injection. In WT mice, blood glucose level returned to control levels by 30min and were significantly lower at 60-min. OxtR KO mice maintained elevated glucose levels at 30-min. WT mice showed a significant increase in insulin levels at 15-min, while OxtR KO mice did not. OxtR was expressed in both insulin and glucagon-positive cells with higher expression in glucagon-positive cells. WT islets showed an increase in intra-islet GLP-1 secretion upon Oxt application. CONCLUSIONS: The study indicates that Oxt may enhance insulin secretion by promoting the secretion of intra-islet GLP-1.