Cyanidin-3-rutinoside stimulated insulin secretion through activation of L-type voltage-dependent Ca channels and the PLC-IP pathway in pancreatic β-cells
Cyanidin-3-rutinoside (C3R) is an anthocyanin with anti-diabetic properties found in red-purple fruits. However, the molecular mechanisms of C3R on Ca-dependent insulin secretion remains unknown. This study aimed to identify C3R's mechanisms of action in pancreatic β-cells. Rat INS-1 cells were used to elucidate the effects of C3R on insulin secretion, intracellular Ca signaling, and gene expression. The results showed that C3R at 60, 100, and 300 µM concentrations significantly increased insulin secretion via intracellular Ca signaling. The exposure of cells with C3R concentrations up to 100 μM did not affect cell viability. Pretreatment of cells with nimodipine (voltage-dependent Ca channel (VDCC) blocker), U73122 (PLC inhibitor), and 2-APB (IP receptor blocker) inhibited the intracellular Ca signals by C3R. Interestingly, C3R increased intracellular Ca signals and insulin secretion after depletion of endoplasmic reticulum Ca stores by thapsigargin. However, insulin secretion was abolished under extracellular Ca-free conditions. Moreover, C3R upregulated mRNA expression for Glut2 and Kir genes. These findings indicate that C3R stimulated insulin secretion by promoting Ca influx via VDCCs and activating the PLC-IP pathway. C3R also upregulates the expression of genes necessary for glucose-induced insulin secretion. This is the first study describing the molecular mechanisms by which C3R stimulates Ca-dependent insulin secretion from pancreatic β-cells. These findings contribute to our understanding on how anthocyanins improve hyperglycemia in diabetic patients.
Publication Source (Journal or Book title)
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
Kongthitilerd, P., Thilavech, T., Marnpae, M., Rong, W., Yao, S., Adisakwattana, S., Cheng, H., & Suantawee, T. (2022). Cyanidin-3-rutinoside stimulated insulin secretion through activation of L-type voltage-dependent Ca channels and the PLC-IP pathway in pancreatic β-cells. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 146, 112494. https://doi.org/10.1016/j.biopha.2021.112494