Cyanidin-3-rutinoside stimulated insulin secretion through activation of L-type voltage-dependent Ca<sup>2+</sup> channels and the PLC-IP<inf>3</inf> pathway in pancreatic β-cells
Issued Date
2022-02-01
Resource Type
ISSN
07533322
eISSN
19506007
Scopus ID
2-s2.0-85120788717
Pubmed ID
34891116
Journal Title
Biomedicine and Pharmacotherapy
Volume
146
Rights Holder(s)
SCOPUS
Bibliographic Citation
Biomedicine and Pharmacotherapy Vol.146 (2022)
Suggested Citation
Kongthitilerd P., Thilavech T., Marnpae M., Rong W., Yao S., Adisakwattana S., Cheng H., Suantawee T. Cyanidin-3-rutinoside stimulated insulin secretion through activation of L-type voltage-dependent Ca<sup>2+</sup> channels and the PLC-IP<inf>3</inf> pathway in pancreatic β-cells. Biomedicine and Pharmacotherapy Vol.146 (2022). doi:10.1016/j.biopha.2021.112494 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/86881
Title
Cyanidin-3-rutinoside stimulated insulin secretion through activation of L-type voltage-dependent Ca<sup>2+</sup> channels and the PLC-IP<inf>3</inf> pathway in pancreatic β-cells
Author's Affiliation
Other Contributor(s)
Abstract
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 β-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 µM concentrations significantly increased insulin secretion via intracellular Ca2+ signaling. The exposure of cells with C3R concentrations up to 100 μM 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 Kir6.2 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 β-cells. These findings contribute to our understanding on how anthocyanins improve hyperglycemia in diabetic patients.
