Mechanism of diabetes development due to dysfunction of unfolded protein response

2016 Fiscal Year Final Research Report

• Project/Area Number: 26430090
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Laboratory animal science
• Research Institution: Nara Institute of Science and Technology
• Principal Investigator: Saito Michiko 奈良先端科学技術大学院大学, バイオサイエンス研究科, 客員准教授 (40379558)
• Research Collaborator: Tsuchiya Yuichi
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 小胞体ストレス / 糖尿病 / インスリン

Outline of Final Research Achievements

The endoplasmic reticulum (ER) is an organelle where newly synthesized secretory and membrane proteins are folded and assembled. Various stresses cause the accumulation of unfolded proteins in the ER, resulting in dysfunction of the ER. This condition is called ER stress. ER stress sensors are activated in pancreatic β cells, and loss of these sensors causes diabetes. Although the function of each sensor has been well studied, their precise roles in animal tissues are largely unknown.
To examine this physiological role of the IRE1α (one of the ER stress sensors) in pancreatic β cells, we generated pancreatic-β-cell-specific IRE1α conditional KO (CKO) mice and IRE1α-CKO insulinoma cell lines. IRE1α CKO mice developed insulin-dependent diabetes. We found that expression of some genes encoding folding enzymes was decreased in the insulinoma cells. From these observations, we concluded that IRE1α was found to be necessary for the folding process of insulin.

Free Research Field

実験動物学、分子生物学