title: Low molecular weight chitosan accelerates glucagon-like peptide-1 secretion in human intestinal endocrine cells via a p38-dependent pathway.
abstract: Chitosan is widely employed as a dietary supplement. Several studies have shown that chitosan possesses an antidiabetic effect. An important intestinal incretin hormone, glucagon-like peptide-1 (GLP-1), is also known to contribute to the amelioration of diabetes. This study investigated whether chitosan possesses an ability in GLP-1 synthesis and secretion in human intestinal cells. Low molecular weight chitosan (LMWC) significantly increases GLP-1 secretion in human intestinal endocrine cells (NCI-H716) in a dose-dependent manner. LMWC could also dose-dependently increase the mRNA expression of proglucagon, a GLP-1 precursor, but did not affect prohormone convertase 3 (PC 3) mRNA expression. LMWC effectively increased the phosphorylation of mitogen-activated protein kinases (MAPK)-p38 and c-Jun N-terminal kinases (JNK), but not extracellular-signal-regulated kinases (ERK). An inhibitor of p38, but not JNK and ERK, significantly reversed the LMWC-increased proglucagon expression. Taken together, LMWC accelerates proglucagon expression and GLP-1 secretion through a p38/MAPK-dependent signaling pathway. These findings suggest that LMWC may provide a strategy for diabetes therapy.
authors.affiliation: Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Shing Hwa
authors.initials: SH
authors.lastname: Liu
authors.forename: Ya Wen
authors.initials: YW
authors.lastname: Huang
authors.forename: Cheng Tien
authors.initials: CT
authors.lastname: Wu
authors.forename: Chen Yuan
authors.initials: CY
authors.lastname: Chiu
authors.forename: Meng Tsan
authors.initials: MT
authors.lastname: Chiang
mesh_terms: D002460:Cell Line; D048271:Chitosan / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D019858:Enteroendocrine Cells / Q000187:drug effects* / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000502:physiology; D008970:Molecular Weight; D010766:Phosphorylation / Q000187:drug effects; D052336:Proglucagon / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D052336:Proglucagon; D052216:Glucagon-Like Peptide 1; D048271:Chitosan; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases