Low Molecular Weight Chitosan Accelerates Glucagon-like Peptide-1 Secretion in Human Intestinal Endocrine Cells via a p38-Dependent Pathway

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.