Development of a new preoperative glycemic control method based on insulin resistance and neutrophil function in chronic hyperglycemic mice.

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K17837
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55050:Anesthesiology-related
• Research Institution: Kobe University
• Principal Investigator: Ueno Kyohei 神戸大学, 医学部附属病院, 医員 (30833131)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 糖尿病 / 好中球機能 / インスリン抵抗性 / PI3K-Akt / NETs

Outline of Final Research Achievements

We investigated whether the PI3K-Akt pathway is involved in the mechanism by which insulin therapy improves neutrophil function in diabetic patients. Chronic hyperglycemic mice with blood glucose levels of 500 mg/dL or higher were created and treated with insulin therapy. The insulin intervention group showed no change in phosphorylated Akt expression compared to the chronically hyperglycemic mice, and the results were not consistent. Since mouse neutrophils have low protein levels, it was considered difficult to examine signaling, so we examined phagocytosis, phosphorylated Akt, and Akt expression using HL60 cells, which differentiate into neutrophil-like cells. The results suggested that increased expression of Akt in differentiated HL60 cells may increase phagocytosis ability of differentiated HL60 cells in vitro.

Free Research Field

麻酔・集中治療

Academic Significance and Societal Importance of the Research Achievements

インスリンは血糖降下作用のほかに、好中球に作用し異物を貪食する能力を増加させたり、過剰な炎症である好中球細胞外トラップの産生を低下させたりする作用を持っている可能性がある。これらのメカニズムには、好中球細胞内のAktの発現が関与する可能性がある。貪食能に関与するAktの発現は、マクロファージや単球での報告はあるが、好中球での報告はほとんどない。糖尿病患者の術前の適切な血糖管理方法を模索するために、感染防御の最前線で機能する好中球の機能の解明は欠かせない。