The elucidation of regulatory mechanisms of glucagon secretion through HSP72 in pancreatic alpha cells.

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K16526
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52010:General internal medicine-related
• Research Institution: Kumamoto University
• Principal Investigator: KITANO SAYAKA 熊本大学, 病院, 医員 (10855745)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: HSP72 / 膵α細胞 / 細胞内ストレス / 糖代謝 / グルカゴン分泌

Outline of Final Research Achievements

Activation of HSP72 in αTC cells and db/db mice decreased glucagon levels in culture medium and blood, and reduced glucagon staining area in the MET group in immunostaining of pancreatic islets. In addition, intracellular stress was attenuated and insulin signaling was improved. These results indicate that HSP72 has a protective effect on pancreatic α-cells. Furthermore, since mice expressing HSP72 specifically in pancreatic α-cells were generated, we plan to further analyze how glucose metabolism is altered by HSP72 in pancreatic α-cells by activating HSP72 in a time- and organ-specific manner.

Free Research Field

代謝内科学分野

Academic Significance and Societal Importance of the Research Achievements

HSP72発現レベルを増強させることによって、生活習慣病や慢性炎症を改善し、糖尿病発症予防から治療まで、さらには細胞保護効果から細小血管合併症の抑制、また心血管系の保護にも働くことから大血管合併症の進行抑制にも寄与できる可能性が期待できる。今回その中でも膵臓における膵β細胞保護作用、インスリン分泌能への作用は解明されつつあるものの、膵α細胞における作用は依然として不明なままである。そこで、今回膵α細胞におけるHSP72の機能が明らかとなれば、膵β細胞におけるHSP72の細胞保護作用も合わせ膵臓のHSP72をターゲットとした創薬へ寄与できる可能性が広がる。