Journal
BIOMEDICINE & PHARMACOTHERAPY
Volume 146, Issue -, Pages -Publisher
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.biopha.2021.112494
Keywords
Cyanidin-3-rutinoside; Insulin secretion; Pancreatic beta-cells; Intracellular Ca2+ signaling; Voltage-dependent Ca2+ channel; PLC-IP3 pathway
Funding
- 90th Anniversary Chulalongkorn University Fund
- Ratchadaphiseksomphot Endowment Fund, Chulalongkorn University
- National Research Council of Thailand (NRCT) [N42A640325]
- LSU-SVM CORP grant
- LSU-SVM CBS Bridging grant
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C3R stimulates insulin secretion by promoting Ca2+ influx via VDCCs and activating the PLC-IP3 pathway. It also upregulates the expression of genes necessary for glucose-induced insulin secretion.
Cyanidin-3-rutinoside (C3R) is an anthocyanin with anti-diabetic properties found in red-purple fruits. However, the molecular mechanisms of C3R on Ca2+-dependent insulin secretion remains unknown. This study aimed to identify C3R's mechanisms of action in pancreatic beta-cells. Rat INS-1 cells were used to elucidate the effects of C3R on insulin secretion, intracellular Ca2+ signaling, and gene expression. The results showed that C3R at 60, 100, and 300 mu M concentrations significantly increased insulin secretion via intracellular Ca2+ signaling. The exposure of cells with C3R concentrations up to 100 mu M did not affect cell viability. Pretreatment of cells with nimodipine (voltage-dependent Ca2+ channel (VDCC) blocker), U73122 (PLC inhibitor), and 2-APB (IP3 receptor blocker) inhibited the intracellular Ca2+ signals by C3R. Interestingly, C3R increased intracellular Ca2+ signals and insulin secretion after depletion of endoplasmic reticulum Ca2+ stores by thapsigargin. However, insulin secretion was abolished under extracellular Ca2+-free conditions. Moreover, C3R upregulated mRNA expression for Glut2 and Kir(6.2) genes. These findings indicate that C3R stimulated insulin secretion by promoting Ca2+ influx via VDCCs and activating the PLC-IP3 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 Ca2+-dependent insulin secretion from pancreatic beta-cells. These findings contribute to our understanding on how anthocyanins improve hyperglycemia in diabetic patients.
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