Molecular mechanisms of pancreatic beta cell proliferarion via endoplasmic reticulum stress responses

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K16411
• 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: Kyoto University
• Principal Investigator: Murakami Takaaki 京都大学, 医学研究科, 助教 (50904017)
• Project Period (FY): 2022-04-01 – 2024-03-31
• Keywords: 糖尿病

Outline of Final Research Achievements

The purpose of this study is to elucidate the role of ER stress response-related factors, mainly ATF6, in pancreatic β-cell proliferation and its possible effects on the amount of living pancreatic β-cells. Although activation of ATF6 and increase of BrdU-positive cells have been reported in isolated islets cultured under high concentration glucose conditions as well as partial pancreatectomy, few islet-specific analyses of pancreatic β-cells have been conducted, and it was necessary to use a pancreatic β-cell-specific experimental system to clarify the role of ATF6 in inducing pancreatic β-cell proliferation Therefore, it was necessary to use a pancreatic beta cell-specific experimental system to elucidate the role of ATF6 in inducing pancreatic beta cell proliferation. The applicant created a pancreatic β-cell-specific ATF6α knockout mouse based on pancreatic β-cell single cell RNA sequencing data.

Free Research Field

糖尿病

Academic Significance and Societal Importance of the Research Achievements

本研究の目的は、膵β細胞増殖におけるATF6を中心としたERストレス応答関連因子の役割を解明するとともに、生体膵β細胞量に与えうる影響とその分子機構を解明することである。本研究では、単一細胞RNAシークエンス解析データを基に、膵β細胞特異的ATF6α欠損マウスを作製した。このマウスを用いた膵β細胞量や膵β細胞増殖能の詳細な解析により、ATF6などERストレス応答経路を標的とし成体膵β細胞増殖を介した膵β細胞量保護効果を有する糖尿病治療の予防・治療法の創出に繋がる新規研究基盤構築への貢献が期待できる。