Role of UBE2E2 in regulating pancreatic beta cell mass

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K17977
• 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: The University of Tokyo
• Principal Investigator: Sakurai Yoshitaka 東京大学, 医学部附属病院, 助教 (70748376)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: インスリン分泌

Outline of Final Research Achievements

In 2010, large-scale Genome-Wide Association Study (GWAS) identified novel susceptibility loci for T2DM. In this study, SNPs in UBE2E2 were associated with T2DM in populations of East Asian descent but not in populations of European descent. To verify its role in pancreatic beta cells, we generated pancreatic beta cell-specific UBE2E2 transgenic mice. Two independent lines exhibited hyperglycemia with decreased insulin secretion during glucose tolerance test. They showed decreased beta cell mass and proliferative capacity of beta cells before weaning, and elevated gene expression of p21 in pancreatic islet cells. Proteome analysis showed a marked decrease in Mesothelin (MSLN), but MSLN knockout mice had normal glucose tolerance.
Overexpression of UBE2E2 in pancreatic beta cells was associated with decreased insulin secretion after glucose loading via a decrease in beta cell mass.

Free Research Field

糖尿病

Academic Significance and Societal Importance of the Research Achievements

本研究に用いるモデルマウスは当研究室で独自に作製されたものであり、類似の研究結果は国内外を含め未だ報告されていない。また、以前より日本人と欧米人の糖尿病の病態は異なることが広く知られているが、本研究結果で明らかになった事象に基づき検討を行うことで、日本人に特徴的な糖尿病発症の素地やメカニズムの一端を解明できるかもしれない。