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https://zone.biblio.laurentian.ca/handle/10219/3794
Titre: | High-fat diet-induced loss of muramyl dipeptide sensitivity |
Auteurs: | Williams, Laura Marie |
Mots clés: | Muramyl dipeptide;glucagon-like peptide-1;Type 2 Diabetes;NOD2;oral glucose tolerance |
Date publié: | 24-aoû-2020 |
Abstrait: | Glucagon-like peptide-1 (GLP-1) is an insulin-stimulating hormone released from enteroendocrine cells. Muramyl dipeptide (MDP) is a peptidoglycan motif which has insulin- sensitizing effects in obesogenic mice by acting through the nucleotide oligomerization domain 2 (NOD2) receptor. We hypothesized that MDP enhances glucose tolerance by inducing intestinal GLP-1 secretion through NOD2 activation. We observed a significant increase in GLP-1 secretion when L-cells were treated with a fatty acid MDP derivative (L18-MDP). Additionally, we demonstrated NOD2 expression in mouse intestine and in L-cells. Two intraperitoneal injections of MDP (5mg/kg) significantly increased fasting total GLP-1 in chow-fed mice; an effect that was lost during the onset of hyperglycemia during a high-fat diet. No improvement in oral glucose tolerance was observed in MDP-treated mice. Finally, we demonstrated in L-cells that hyperglycemic conditions reduce NOD2 and GLP-1 mRNA expression. Together these findings suggest MDP may play a role in enhancing GLP-1 during euglycemia but loses its ability to do so in hyperglycemia. |
URI: | https://zone.biblio.laurentian.ca/handle/10219/3794 |
Apparaît dans les collections: | Biology - Master's Theses Master's Theses |
Fichiers dans cet item:
Fichier | Description | Taille | Format | |
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Laura Williams MSc thesis July 13th.pdf | 1.73 MB | Adobe PDF | Parcourir/Ouvrir |
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