Function-structure relationship; role of the islet Schwann cells

2018 Fiscal Year Final Research Report

• Project/Area Number: 26461346
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Metabolomics
• Research Institution: Jikei University School of Medicine
• Principal Investigator: Sasaki Takashi 東京慈恵会医科大学, 医学部, 教授 (90205849)
• Co-Investigator(Kenkyū-buntansha): 藤本 啓 東京慈恵会医科大学, 医学部, 准教授 (40372974)
• Research Collaborator: Nemoto Masami ; Kouno Midori ; Yoshizawa Yukio
• Project Period (FY): 2014-04-01 – 2019-03-31
• Keywords: 膵島障害 / インスリノーマ / 三次元培養法 / インスリン分泌

Outline of Final Research Achievements

In this study, with the aim of basic research to understand the mechanism of exhaustion of islet function that causes diabetes, we analyzed the interaction between cultured Schwann cells and cultured murine β cells as well as cells isolated from human insulinoma tissue. We focus on what kind of cells consisting the microenvironment of the islet, and whether the cells have antioxidant ability to defense from the oxidative stress that causes the dysfunction, and gene mutations that affect secretory ability. For these purpose, we analyzed the influence of oxidative stress on the cells of pancreatic islets by cultured cell lines, identification of a signal transduction system between intra-islet cells within a three-dimensional culture system, and gene mutation of human pancreatic insulinoma cells. We found that the mechanism of coordination in the islet microenvironment as well as the involvement of specific genes have been estimated.

Free Research Field

膵内分泌

Academic Significance and Societal Importance of the Research Achievements

酸化ストレスや特定の遺伝子異常による膵内分泌機能、すなわちブドウ糖応答性インスリン分泌機能の低下は糖尿病の原因と考えられている。本研究ではその発生メカニズムを明らかにする上で、特に膵島の三次元的な構成と機能の連関、構成細胞として膵島を被覆するシュワン細胞をも考慮に入れた点がユニークな研究であった。また、低重力培養装置を用いた三次元培養法による細胞間の相互作用の検討、ならびにヒトインスリノーマ細胞におけるインスリン分泌異常を起こす遺伝子異常に焦点を当てた点は、方法論としても新規のもので、当該分野に与えるインパクトも大きい。