Targeting a GLP-1R-agmatine axis for PCOS

GLP-1R agonism or inhibition of the metabolite agmatine could help treat PCOS by counteracting Bacteroides vulgatus-induced activation of the transcription factor FXR in intestinal epithelial L cells, which inhibits GLP-1 secretion and thus promotes insulin resistance that drives ovarian dysfunction.

GLP-1 levels were lower in serum from PCOS patients than in serum from healthy individuals, and lower GLP-1 levels were negatively correlated with androstenedione levels, the ratio of luteinizing hormone to follicle stimulating hormone levels, and HOMA-IR index. Previous studies showed PCOS patients have a higher abundance of Bacteroides in their gut than healthy individuals. ...