Elucidation of the diabetes onset mechanism mainly on autophagy and human islet amyloid polypeptide

2014 Fiscal Year Final Research Report

• Project/Area Number: 25860758
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Metabolomics
• Research Institution: Juntendo University
• Principal Investigator: KOMIYA Koji 順天堂大学, 医学部, 助教 (50385077)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: 糖尿病 / オートファジー / 膵島アミロイド蛋白 / 膵β細胞

Outline of Final Research Achievements

In this study, we investigated the synergistic role of human IAPP (hIAPP) and autophagy dysfunction in the pathogenesis of diabetes. In the previous study we reported that reduced autophagic acitivity in beta cells caused impaired glucose tolerance. Physiological expression of human IAPP using hIAPP knockin strategy further exacerbated glucose intolerance of mice with beta-cell specific autophagy deficiency. Induction of hIAPP in insulinoma cells and in hIAPP knockin mice resulted in inhibition of beta cell proliferation associated with decreased phosphorylation of insulin receptor. These results suggested that inhibition of insulin signaling by hIAPP may be involved in the loss of compensatory proliferation of beta cells and impaired glucose tolerance.

Free Research Field

代謝内分泌内科学