Establishment of pancreatic islet morphological model describing pathogenic mechanism of type 2 diabetes by human pancreatic histological analysis

2015 Fiscal Year Final Research Report

• Project/Area Number: 25461350
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Metabolomics
• Research Institution: Osaka University
• Principal Investigator: Kozawa Junji 大阪大学, 医学(系)研究科(研究院), 助教 (80513001)
• Co-Investigator(Kenkyū-buntansha): IMAGAWA Akihisa 大阪大学, 医学系研究科, 准教授 (80373108) ; IWAHASHI Hiromi 大阪大学, 医学系研究科, 寄附講座准教授 (60397627)
• Co-Investigator(Renkei-kenkyūsha): EGUCHI Hidetoshi 大阪大学, 医学系研究科, 准教授 (90527756)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 膵島 / インスリン分泌能 / インスリン抵抗性 / 膵β細胞 / 膵α細胞

Outline of Final Research Achievements

Patients who had undergone pancreatic resection in Osaka University Hospital were enrolled. They were classified into those with four different stages (normal glucose tolerance, impaired glucose tolerance, newly diagnosed diabetes, long-standing type 2 diabetes) of glucose intolerance, and their pathological conditions were evaluated. Beta-cell mass decreased as the glucose intolerance advanced, and the decrease was associated with the deterioration of insulin secretory capacity. In patients with long-standing type 2 diabetes, alpha-cell mass increased compared with those in the other groups. The increase of alpha-cell mass was accompanied by increase of Ki67-positive ratio in alpha-cells and was associated with glycemic control. Phenotypic changes in pancreatic endocrine cells, including dedifferentiation and transdifferentiation, might partly contribute to alpha-cell mass with worsening glucose tolerance.

Free Research Field

内分泌・代謝