Polysaccharides from Portulaca oleracea L. regulated insulin secretion in INS-1 cells through voltage-gated Na+ channel

[Display omitted] •The present work is the first to present direct evidence of POP’s modulation on insulin secretion/production through VGSC in INS-1 cells.•POP regulated insulin secretion/production by improving the survival of INS-1 cells.•POP regulated insulin secretion/production in INS-1 cells were mediated by VGSC through its change of the communication of cell membrane and mitochondria including intracellular Ca2+ releasing, ATP metabolism and cell/mitochondrial membrane potential.•POP promoted insulin secretion/production by regulating the expression levels of Nav1.3 and Nav1.7 in INS-1 cells. The present study was undertaken to determine the involvement of voltage-gated Na+ channel (VGSC) and other mechanism related to insulin secretion in polysaccharides from Portulaca oleracea L. (POP)-induced secretion of insulin from insulin-secreting β-cell line cells (INS-1) cells. Our results showed that the concentration of insulin both in culture medium and inside INS-1 cells were increased under the existing of different concentration of glucose by POP or TTX, respectively. However, the effect POP on insulin secretion and production were blocked by TTX, a VGSC blocker. Meanwhile, POP improved the mitochondrial membrane potential (Δψm), increased adenosine triphosphate (ATP) production, depolarized cell membrane potential (MP) and increased intracellular Ca2+ levels ([Ca2+]i). Furthermore, POP treatment increased the expression level of Nav1.3 and decreased the expression level of Nav1.7. TTX treatment decreased the expression level of Nav1.3 and Nav1.7. On the other hand, POP also elevated the survival of INS-1 cells. These results suggested that POP induced-secretion/production of insulin in INS-1 cells were mediated by VGSC through its change of function and subunits expression and subsequent VGSC- dependent events such as change of intracellular Ca2+ releasing, ATP metabolism, cell membrane and mitochondrial membrane potential, and also improvement of INS-1 cell survival. Meanwhile, our data indicated the potentiality of developing POP to be a drug for diabetes treatment and VGSC as a therapeutic target in diabetes treatment is valuable to be investigated further.