|Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
|Outline of Final Research Achievements
To identify novel small-molecules of insulin secretion regulator, we examined high-throughput screening analysis to identify chemical compounds that activate (or inhibit) insulin secretion in pancreatic beta-cells and identified several kinds of compounds as activator (or inhibitor) of insulin secretion. Pull-down assay experiment using chemical compound conjugated magnetic beads revealed that one of the activators binds to mitochondrial protein, VDAC. siRNA-mediated depletion of VDAC1 in INS1 832/13 cells reduced increase of insulin secretion by the activator, and in addition, intracellular ATP level is increased by the activator in beta-cells. These results demonstrate that glucose-stimulated insulin secretion is up-regulated by increase of intracellular ATP level through binding of the novel activator to VDAC protein.