| Summary: | 碩士 === 國立臺灣海洋大學 === 食品科學系 === 100 === Impaired glucose regulation in rats fed with chitosan can reduce plasma glucose and increase plasma glucagon-like peptide-1 (GLP-1) levels, but the main mechanisms involved are unknown. GLP-1 is capable of regulating several biological actions in peripheral tissues including slowing of gastric emptying, stimulation of insulin secretion and pancreatic -cells proliferation, and increasing of muscle glucose uptake, storage, and raising of insulin sensitivity; therefore, GLP-1 may be as an adjunctive therapy in subjects with type 2 diabetes mellitus. In this study, we used a human cellular model for studying the regulation of GLP-1 secretion and mechanism by chitosan. A human intestinal cell line, NCI-H716 cells, was used in all experiments. NCI-H716 cells were incubated with various concentrations of low molecular weight chitosan (25, 50, 100 and 200 g/ml) in the presence or absence of insulin for various time intervals to investigate the effects of chitosan on action and mechanism of GLP-1 secretion. As shown in the results, low molecular weight chitosan significantly increased the protein expressions of phosphorylated JNK and phosphorylated p38 MAPK and the mRNA expression of proglucagon, a precursor of GLP-1, and then enhanced GLP-1 secretion. Inhibitors of JNK and p38 MAPK lowered the proglucagon and prohormone convertase 3 mRNA expressions, indicating that GLP-1 synthesis was regulated by JNK and p38 MAPK signaling pathway. Taken together, these results suggest that chitosan may enhance GLP-1 synthesis in intestinal cells via the up-regulation of phosphorylations of JNK and p38 MAPK protein and proglucagon and PC3 mRNA expression, which may further improve the impaired glucose regulation in diabetic animals.
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