Alshehri, Amal2020-09-282020-09-282020-08-13https://laurentian.scholaris.ca/handle/10219/3566Type 2 diabetes (T2D) accounts for 90% of all cases of diabetes, and it is one of the world’s most threatening chronic and metabolic diseases in the world. Researchers have been investigating the possible links between the glucagon-like peptide1 (GLP-1) incretin hormone and bacterial metabolites in the gut in order to improve T2D treatments. In this study, I hypothesized that muramyl dipeptide (MDP) enhances the release of GLP-1 to improve hyperglycemia. Various muropeptides were tested in GLP-1 secreting cell lines (NCI-H716 and GLUTag) for their ability to regulate hormone secretion. The intracellular mechanism of lipid-modified L18MDP was examined via western blot and pharmacological inhibition. Pilot studies using siRNA for the MDP receptor NOD2 were completed. GLP-1 secretion was significantly induced by different concentrations of L18MDP in the two cell lines, (5, 10 µg/ml) in GLUTag and (10 µg/ml) in NCIH716. Treatment did not affect cell lines viability. The p38 MAPK signaling pathway was slightly stimulated at the 10-minute L18MDP treatment as was demonstrated by western blot. Pharmacological NOD2 inhibition with GSK717 at different doses (5, 10 µM) failed to block the L18MDP stimulation of GLP-1 secretion in GLUTag and NCI-H716 cell lines. This work demonstrates that L18MDP can significantly stimulate GLP-1 release; however, future work will be required to resolve the precise mechanismenGlucagon-like peptide 1GPL-1muramyl dipeptideMDPL18MDPp38 MAPKThesis