| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Outline of Final Research Achievements |
Phogrin is a transmembrane protein that localizes on secretory granules in pancreatic β-cells. We previously showed that phogrin participates in molecular interactions with insulin receptors (IR) to regulate insulin receptor substrate 2 (IRS2) protein stability and in turn glucose-promoted β-cell growth. Glucose is a principal regulator of β-cell survival and growth as well as insulin secretion. Despite the growing evidence for the significance of the IR/IRS2-mediated signaling pathways in β-cells, whether secreted insulin acts in an autocrine fashion remains controversial. We showed that phogrin-deficient mice fed a fat diet have defects in β-cell compensatory growth. This is likely because phogrin binds to IR only at conditions that are needed for β-cell expansion. We identified a new phogrin partner, and its binding of phogrin inhibits phogrin-IR interactions. This study represents the first report of a switching regulator of autocrine insulin action in pancreatic β-cells.
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