The role of PHD3 in hypoxic response of pancreatic beta cells

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K17538
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 54040:Metabolism and endocrinology-related
• Research Institution: Kumamoto University
• Principal Investigator: TSUYAMA TOMONORI 熊本大学, 大学院生命科学研究部(医), 特任助教 (10845960)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: 低酸素 / 糖尿病

Outline of Final Research Achievements

We have recently identified prolyl-hydroxylase 3 (PHD3) as highly up-regulated genes in hypoxic β-cells. This study revealed the role and expression of PHD3 in hypoxic and diabetic β-cells as follows. (1) In consistent with the occurrence of hypoxia in the β cells of type 2 diabetes (T2D) mice, these cells show highly upregulation of Phd3 expression. (2) β-cell-specific Phd3 knockout mice in T2D mice background were established. (3) PHD3 deletion in β-cells improved glucose tolerance in T2D mice.

Free Research Field

低酸素

Academic Significance and Societal Importance of the Research Achievements

２型糖尿病の病態に膵β細胞における低酸素ストレスが関与している可能性が示唆されているが、その具体的なメカニズムは知られていない。本研究ではβ細胞における低酸素応答因子であるPHD3が糖尿病病態において血糖値に影響を及ぼす重要な因子であることを明らかにした。今後PHD3の機能の詳細を明らかにしていくことで、２型糖尿病の病態解明や新たな治療戦略の開発につながることが期待できる。