Heterogeneity of pancreatic islets

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K16240
• 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: Yokohama City University
• Principal Investigator: Shirakawa Jun 横浜市立大学, 医学部, 講師 (70625532)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Keywords: 糖尿病 / 膵β細胞量 / 膵島 / 不均一性 / 分化転換 / 脱分化

Outline of Final Research Achievements

Recent studies showed subpopulation of pancreatic β cells in the context of functional and phenotypic heterogeneity. Distinct β cell subpopulations potentially have unique functional identity. We topologically divided pancreas into a head (right side, nestled in the curve of the duodenum), body, and tail (left side in close proximity with the spleen) region in mice. Then, we compared head islets with tail islets histologically and functionally. Tail islets contained significantly higher proportion of α-cells. Glucose-stimulated insulin secretion was significantly greater in tail islets than in head islets, while β cells in head islets showed higher response to GLP-1. The results of gene expression microarray analysis and proteomics analysis indicated that some functional genes including pancreatic progenitor markers were differentially expressed between head and tail islets. Thus, pancreatic islets harbor functional diversity in terms of various aspects of β cell function.

Free Research Field

糖尿病内科学

Academic Significance and Societal Importance of the Research Achievements

本研究では、膵β細胞の不均一性を越えて、膵島での不均一性の存在と、それらの分子機構が明らかになり、新規に分類された膵島を対象とした膵β細胞機能不全のメカニズム解明が可能となる。さらにこれらの研究成果をヒトに応用していくことにより、目的とする機能的特性をもつ膵島のみを単離し、膵島のサブタイプに特化した膵島移植の実施や、iPS細胞等の幹細胞から、機能的膵β細胞量の回復に最適な機能的特性を有する膵島サブタイプの創出への発展が期待される。