Author(s): Guo LX, Liu JH, Yin F
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Abstract AIM: Type 2 diabetes mellitus is characterized by lack of, or relative deficiency in, insulin productions and insensitivity of target tissues to insulin. Improvement of β-cell functions is a potential strategy for the clinical management of this disease. We reported before that geniposide improved glucose-stimulated insulin secretion with the activation of glucagon-like peptide 1 receptor (GLP-1R) in INS-1 pancreatic β cells, but the cell signaling mechanism of geniposide regulating glucose-stimulated insulin secretion (GSIS) in β cells is so far poorly understood. MATERIALS AND METHODS: Effect of LY294002, a specific inhibitor of PI3K, on GSIS in the presence or absence of geniposide in INS-1 cells. In addition, the differential protein expression of geniposide treated INS-1 cells was examined by Western blot. RESULTS: After pretreatment with 10 µM LY294002 for 1 hour, the insulin secretion induced by geniposide was partly abolished in INS-1 cells. After treatment with geniposide, the phosphorylation of PDK1 and Akt473 increased gradually to the maximum at 60 minutes or 120 minutes respectively. Furthermore, geniposide also inhibited the phosphorylation of downstream target GSK3β, and this effect was counteracted by preincubation with LY294002. And the expression of GLUT2 was increased after treatment with different doses geniposide. CONCLUSIONS: Geniposide increases insulin secretion in pancreatic β cells in a PI3K dependent mechanism potentially through increased GLUT2 protein levels.
This article was published in Eur Rev Med Pharmacol Sci
and referenced in Medicinal Chemistry