Elucidation of a new mechanism of action of GLP-1 focusing on pancreatic islet blood flow - Investigation by in vivo imaging -

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K16360
• 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: Kawasaki Medical School
• Principal Investigator: Kimura Tomohiko 川崎医科大学, 医学部, 講師 (50454830)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 膵島血流 / GLP-1 / 虚血 / 糖尿病

Outline of Final Research Achievements

Three minutes after administration of Liraglutide（Lira）to the diabetic model, the vascular volume around the pancreatic islets was significantly expanded by about 20%. Blood flow velocity also increased. Chronic administration improved blood glucose levels in the Lira group compared to the control group. In vivo imaging showed that the volume of pancreatic islet blood vessels was higher in the Lira group. Pimonidazole staining and CD31 staining also supported this finding. Furthermore, in the Lira group, NO production in pancreatic islets was significantly increased. Regarding pancreatic islet gene expression, the expression of Hif1α, an ischemic marker, was low in the Lira group, and its downstream factors were also decreased, suggesting that the increase in NO caused by chronic Lira administration protected pancreatic islets from ischemia.

Free Research Field

糖尿病

Academic Significance and Societal Importance of the Research Achievements

糖尿病治療薬であるGLP-1受容体作動薬は、単に血糖降下薬としてではなく、動脈硬化性疾患や腎障害を合併する2型糖尿病患者への使用が学会アルゴリズムからも推奨されている。これらのメカニズムの1つにGLP-1受容体作動薬による血管への直接効果が関与していることが我々を含め、報告されてきている。今回の検討では、糖尿病状態における膵ラ氏島の血流をGLP-1が有意に増加させることを確認しており、これはGLP-1によるインスリン分泌機序の1つであると示唆される。GLP-1は膵β細胞を虚血から保護することにより機能障害を抑制しており、新規治療法の確立に寄与する可能性がある。