Role of protein O-GlcNAcylation in physiology and diabetes

2021 Fiscal Year Final Research Report

• Project/Area Number: 18H02862
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 54040:Metabolism and endocrinology-related
• Research Institution: Shiga University of Medical Science
• Principal Investigator: Maegawa Hiroshi 滋賀医科大学, 医学部, 教授 (00209363)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: 糖尿病 / 糖尿病合併症 / タンパク翻訳後修飾

Outline of Final Research Achievements

The physiological role of the O-GlcNAcylation, a post-translational modification of proteins, in diabetes and diabetic complication-related organs and the relationship between its abnormalities and diabetes development. The results show that O-GlcNAc modification contributes to lipogenesis in white adipose tissue, exercise-induced glucose uptake and utilization in skeletal muscle, regulation of lipid absorption from the intestine, regulation of glucose absorption via SGLT1 expression from the intestine, and fatty acid oxidation and ATP production during fasting in the renal proximal tubules, and that abnormalities in these functions contribute to the development of abnormal glucose metabolism and diabetic kidney disease.

Free Research Field

糖尿病

Academic Significance and Societal Importance of the Research Achievements

糖尿病ならびにその合併症は、患者さんのQOLを大きく損なう疾患であり、肥満患者数の増加や高齢化が急速に進む我が国において、その有病率の上昇が大きな社会問題の一つとなっている。今回の研究により、タンパク質の翻訳後修飾の一つであるO-GlcNAcylationの異常が糖代謝制御や糖尿病状態での合併症進展に寄与することが明らかとなり、その機能調節が糖尿病や糖尿病合併症に対する新たな治療標的となる可能性が示された。今後の研究の発展により、糖尿病患者さんの健康寿命延伸に対する新たな治療法の開発が期待される。