Quantification of dynamics of secretory granules and study of regulatory mechanism

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K07280
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 48020:Physiology-related
• Research Institution: Kitasato University
• Principal Investigator: Takahashi Noriko 北里大学, 医学部, 教授 (60332178)
• Co-Investigator(Kenkyū-buntansha): 畠山 裕康 北里大学, 医学部, 准教授 (00619067)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 内分泌 / 膵島 / インスリン / 蛍光 / 共焦点顕微鏡 / 糖尿病

Outline of Final Research Achievements

Insulin secretion plays an important role in glucose homeostasis. The mobilization of insulin granules is one of the target step in regulating secretion; however, techniques for precise quantification of the mobilization process with high spatiotemporal resolution remain insufficient. We propose an approach for assessing insulin granule movement based on single molecule imaging of insulin granule membrane proteins labeled with Quantum dot fluorescent nanocrystals or fluorescence such as TMR. The unique regulatory mechanism associated with insulin granule behavior. Pharmacological inhibition of microtubules and the F-actin cytoskeleton revealed that microtubule dynamics and F-actin have the roles on insulin granule movement. These cytoskeleton regulates insulin granule movement on distinct time scales. Our method provides quantitative information regarding insulin granule mobilization and its cytoskeletal dependence.

Free Research Field

生理学

Academic Significance and Societal Importance of the Research Achievements

インスリンは糖代謝や成長に深く関わる膵ホルモンで、その分泌不全は糖尿病の主成因の一つである。日本における糖尿病患者数は予備群を含めると2,000万人にのぼる。近年、ゲノムワイド関連解析で糖尿病の疾患感受性遺伝子が検討され、膵臓の発生や膵β細胞と関連する遺伝子領域が複数報告され、病態へ及ぼす影響が示唆される。糖尿病発症時の段階で、食後早期のインスリン分泌不足が確認される患者が多く、分泌の全貌の解明は社会的にも重要課題であり、本研究は基礎的な知見を提供し、糖尿病治療薬の開発や薬物副反応の解釈にも活用可能と考える。