Endocrine Abstracts

The increasing prevalence of obesity and type 2 Diabetes Mellitus (T2DM) is a worldwide health concern. Existing therapeutic approaches face the challenge of side effects and low patient adherence. Therefore, novel treatments are still required. The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor expressed in different cell types and is thought to be involved in inflammatory responses and regulating endothelial barrier integrity. Indole is an organic compound generated following gut microbial catabolism of L-tryptophan. Indole and its derivatives are AhR ligands, and their production has been reported to have a negative association with the incidence of T2DM. Activating AhR by indole derivatives is associated with enhanced insulin sensitivity in mice. Previous studies have found that indole can promote the acute secretion of glucagon-like peptide-1 (GLP-1) and the proliferation of GLP-1 secreting cells, and thereby improve glucose tolerance both acutely and in the longer term. However, being considered as an experimental agent, the potential of indole as dietary supplement is restricted. Indole-3-Carbinol (I3C) is a derivative of indole that can be commonly found in cruciferous plants. In this study, the acute glucoregulatory effect of I3C was examined. Enteroendocrine STC-1 cells were cultured and different concentrations of I3C applied. Intraperitoneal glucose tolerance test was performed in mice to elucidate the effect of oral administration of I3C in vivo. Our results suggest that I3C can stimulate the secretion of GLP-1 from STC-1 cells in-vitro with 10μM having the most significant effect. Oral administration of I3C significantly improved the glucose tolerance acutely in vivo, but unlike indole, this effect did not persist for several days. Future research will focus on the mechanism underpinning the glucoregulatory effects of I3C, whether they are dependent on AhR signalling, and whether chronic treatment with I3C has the potential to treat metabolic disease.