Role of O-GlcNAcylation in the Intestinal epithelial cells

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K08998
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54040:Metabolism and endocrinology-related
• Research Institution: Shiga University of Medical Science
• Principal Investigator: Ugi Satoshi 滋賀医科大学, 医学部, 講師 (20378483)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 糖鎖修飾 / 腸管 / SGLT1

Outline of Final Research Achievements

To elucidate the effects of O-GlcNAcylation in the intestinal epithelium on nutrient absorption and glucose metabolism, we generated intestinal epithelial cell-specific Ogt gene-deficient mice and examined their phenotype. Ogt-VKO mice showed low body weight, hypoglycemia, and suppressed glucose elevation in an oral glucose tolerance test. We found that SGLT1 expression was downregulated in the small intestine. Furthermore, in an enteroendocrine cell-line STC-1 cells, increasing or decreasing O-GlcNAcylation resulted in a similar change in SGLT1 expression as in the KO mice, suggesting that O-GlcNAcylation is involved in carbohydrate absorption in the intestinal tract.

Free Research Field

糖尿病

Academic Significance and Societal Importance of the Research Achievements

消化管を介した糖吸収が、全身の代謝に関わるという点で画期的である。O-GlcNAc修飾は腸管内の糖質を感知することで、PKA-CREBを介してSGLT1の発現を調整しており、O-GlcNAc修飾を介したグルコース吸収の抑制は肥満、糖尿病の新しい治療法につながる可能性があると考えられた。