The pathophysiological role of pancreatic beta-cell hypoxia in the progression of diabetes

2015 Fiscal Year Final Research Report

• Project/Area Number: 26860697
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Metabolomics
• Research Institution: Kumamoto University
• Principal Investigator: SATO Yoshifumi 熊本大学, 大学院生命科学研究部(医), 助教 (90622598)
• Research Collaborator: YAMAGATA Kazuya 熊本大学, 大学院生命科学研究部, 教授 (70324770) ; INOUE Masahiro 大阪府立病院機構大阪府立成人病センター, 生化学部門, 部長 (10342990) ; KONDOH Shinae 東京工業大学, 生命理工学研究科, 教授 (40314182)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Keywords: 糖尿病 / 低酸素 / 膵β細胞

Outline of Final Research Achievements

The islets (pancreatic beta-cells) of a diabetic mouse become hypoxic. However, how the beta cells become hypoxic under diabetic conditions and what kinds of molecules are related to the beta-cell dysfunction by hypoxia, which still remain unclear. In this study, we generated hypoxia-imaging mice to monitor islet hypoxia in diabetes by crossbreeding an oxygen dependent domain (ODD)-Luciferase transgenic (Tg) mouse with diabetes model mice (ob/ob or db/db mouse). Furthermore, we found that beta-cell hypoxia causes less ATP production by reduced mitochondrial complex Ⅰactivity and abnormal beta-cell gene expression patterns, which results in reduced insulin secretion. And Hypoxia-inducible factor(HIF)-1, a master regulator in hypoxia response didn't contribute to the dysregulated gene expression and impaired insulin secretion by hypoxia. From this aspect, further studies are needed to clarify a HIF-1-independent hypoxia response pathway in beta-cells.

Free Research Field

医歯薬学