New strategy of type 2 diabetes treatment to improve pancreatic beta cell dedifferentiation

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K16222
• 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: Gunma University
• Principal Investigator: Ishida Emi 群馬大学, 医学部附属病院, 助教 (80806357)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 2型糖尿病 / 膵β細胞機能不全 / 脂肪肝

Outline of Final Research Achievements

In diabetic patients, pancreatic beta cells gradually lose the ability to secrete insulin, and this phenomenon is called beta cell failure. Recently, beta cell dedifferentiation was proposed as one of the cause of beta cell failure. We seeked a novel diabetes treatment strategy for improving the beta cell dedifferentiation. In previous study, calorie restriction prevented the beta cell dedifferentiation in obese mice model (db/db). First, we focused on the nutrition balance during calorie restriction. We made the high fat/low carbohydrate food (HF) and low fat/high carbohydrate food (HC), and fed db/dbs with each food with calorie restriction. Both food improved the body weight and glucose tolerance, but HF food more improved the beta cell dedifferentiation and fatty liver. HC food elevated the gene expression related to fat synthesis, and increased lipid contents in liver. It suggested that the nutrition balance in food and fat in liver affected the beta cell function.

Free Research Field

内分泌代謝学

Academic Significance and Societal Importance of the Research Achievements

2型糖尿病ではβ細胞機能不全が起こるため、長年罹病していると徐々にインスリンが必要になる病態に陥っていくことは昔から知られていた。しかしながら、β細胞機能不全の分子メカニズムが解明されてきたのはここ5年くらいのことであり、いまだにβ細胞機能不全を予防・改善する、ある意味糖尿病の完治を目指す治療というのは開発途上である。本研究では、提唱されたβ細胞機能不全のうち、β細胞脱分化に着目し、それが摂取する栄養素バランスや、肝での脂肪代謝によって影響される分子メカニズムの一端を解明した。この研究から、β細胞機能を維持するための食事療法などの新規糖尿病治療戦略が生まれると考えられる。