Consumption of carotenoid-rich Momordica cochinchinensis (Gac) aril improves glycemic control in type 2 diabetic mice partially through taste receptor type 1 mediated glucagon-like peptide 1 secretion

Incretin-based therapies are widely used to improve glycemic control and β cell dysfunction in the treatment of type 2 diabetes. (Gac fruit), a nutritious melon cultivated in many regions, has underexplored health benefits, particular its edible aril. This study comprehensively investigates the stimulatory effect of Gac aril on glucagon-like peptide 1 (GLP-1) secretion, identifies the responsible active constituents, and explores the underlying mechanisms related to its anti-diabetic effects. GLP-1-secreting STC-1 intestinal L cells were used to assess bioactivity and molecular mechanisms. Additionally, the anti-diabetic effects of Gac aril consumption were evaluated using type 2 diabetic mice induced by a high fat diet and streptozotocin injection, with or without GLP-1 receptor expression. The results demonstrated that Gac pulp and aril stimulated GLP-1 secretion, while Gac seeds did not. β-Carotene, a major constituent of Gac aril, was identified as the key mediator of GLP-1 secretion sweet taste receptor-mediated signaling in STC-1 cells. Dietary intake of Gac aril significantly improved fasting blood glucose, glucose tolerance, insulin sensitivity, β-cell function, and hemoglobin A1c in type 2 diabetic mice. GLP-1 levels increased 2-fold, and decreased levels of ghrelin and adiponectin were restored. The anti-diabetic effects were partially diminished in GLP-1 receptor knockout mice, suggesting Gac aril's effects are mediated, in part, through GLP-1. In conclusion, Gac aril consumption may provide health benefits for managing type 2 diabetes, partially by enhancing endogenous GLP-1 levels.