2301-PUB: The Role of Muramyl Dipeptide in Glucagon-Like Peptide-1 Regulation

Abstract

The host’s intestinal microbiota contributes to endocrine and metabolic responses, but a dysbiosis in this environment can lead to obesity and insulin resistance. A new area a research is focused on understanding how bacterial metabolites contribute to intestinal glucagon-like peptide-1 (GLP-1) release. Muramyl dipeptide (MDP) is a bacterial cell wall component which has been shown to improve insulin sensitivity and glucose tolerance in diet-induced obese mice. The purpose of this study was to understand MDP’s mechanism of action in glucose regulation. We hypothesized that MDP enhances glucose tolerance by inducing intestinal GLP-1 secretion. We observed a significant increase (P<0.001, n=7) in GLP-1 secretion when mouse L-cells were treated with an MDP derivative at 10ug/ml. Using fluorescent immunohistochemistry and RT-PCR we located MDP’s receptor, nucleotide oligomerizing domain 2 (NOD2), in mouse intestine and mouse L-cells. In mice, two intraperitoneal injections of MDP (5mg/kg body weight) or PBS caused a significant increase (P=0.0009, n=15-19) in fasting total GLP-1. Understanding how bacterial products influence GLP-1 secretion and subsequent insulin release, could be translated into novel treatments options for improving glucose regulation in metabolic disease. Disclosure L. Williams: None. A. Alshehri: None. S. Mustafa: None. J. Gagnon: None. Funding Natural Sciences and Engineering Research Council of Canada (2016-05905)