trategy of prevention and amelioration of atherosclerosis caused by repeated postprandial hyperglycemia

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K19899
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Research Field: Health science and related fields
• Research Institution: University of Yamanashi
• Principal Investigator: MOCHIZUKI Kazuki 山梨大学, 大学院総合研究部, 教授 (80423838)
• Co-Investigator(Kenkyū-buntansha): 針谷 夏代 山梨学院大学, 健康栄養学部, 准教授 (80732784)
• Project Period (FY): 2017-06-30 – 2020-03-31
• Keywords: 食後高血糖 / 2型糖尿病患者 / ミグリトール / 末梢血白血球 / S100タンパク質 / 単球 / 炎症関連遺伝子 / ヒストン修飾

Outline of Final Research Achievements

In this study, we examined whether repeated postprandial hyperglycemia is imprinted as epigenetic modifications in innate leukocytes such as neutrophils and monocytes, and metabolic cells and promotes the risk of the complications such as arteriosclerosis and steatohepatitis. As a result, a transient increase in blood glucose induced expression of inflammation-related genes in innate leukocytes and reduced expression of genes involved in reactive oxygen species elimination in liver parenchymal cells. In addition, our data suggests that mRNAs of inflammation-related genes in peripheral leukocytes are candidates of biomarkers predicting onset of complications including arteriosclerosis. Furthermore, epigenetic memories such as histone acetylation and methylation are involved in expression changes of the above genes.

Free Research Field

栄養学

Academic Significance and Societal Importance of the Research Achievements

本研究の学術的意義は、食後高血糖の反復による動脈硬化病巣の形成には、好中球や単球等の自然免疫細胞の活性化が関与する可能性が高いこと、自然免疫細胞の活性化には、エピジェネティック制御が関与する可能性が高いことを見出した点である。社会的意義は、本研究で発見した食後高血糖の反復によりmRNA発現が変動する末梢血白血球における遺伝子は動脈硬化発症などの糖尿病合併症の発症進展のバイオマーカーになりうることを見出した点である。