Poster Topical Area: Dietary Bioactive Components
Location: Hall D
Poster Board Number: 380
Objectives: Insulin resistance and β-cell dysfunction are the hallmarks of type 2 diabetes (T2D). The incretin hormone glucagon-like peptide-1 (GLP-1), which is secreted from intestinal L-cells, plays a critical role in maintaining glycemic homeostasis via potentiating glucose-stimulated insulin secretion (GSIS) and promoting β-cell proliferation and survival. Therefore, targeting L-cells for promoting its secretory function could be an effective strategy for treating and preventing T2D. The present study was aimed at identifying bioactive small molecules targeting intestinal GLP-1 secretion to prevent and treat T2D. Here, we report that olive-derived elenolic acid is a potent agonist for GLP-1 secretion.
Methods: GLUTag L-cells and primary mouse ileum crypts were incubated with various concentrations of elenolic acid. GLP-1 released into supernatants was measured using an ELISA kit. Intracellular [Ca2+] was determined using Fluo-4AM.
Results: Elenolic acid dose dependently stimulated GLP-1 release in both clonal L-cells and primary ileum crypts, with 10 µM inducing maximal effect. In addition, elenolic acid induced a rapid intracellular Ca2+ increase. Inhibition of phospholipase C (PLC) ablated elenolic acid-stimulated intracellular Ca2+ release and GLP-1 secretion in L-cells. Consistently, elenolic acids elevated production of inositol trisphosphate in the cells, indicating that elenolic acid activates PLC. Moreover, elenolic acid-triggered GLP-1 secretion from L-cells was blocked by YM-254890, a Gαq inhibitor. In vivo, oral administration of elenolic acid to mice significantly reduced hyperglycemia and glucose tolerance in type 2 diabetic mice.
Conclusions: These data provide evidence that elenolic acid might be a novel anti-diabetic agent through promoting endogenous GLP-1 secretion.