Homeostatic system mediated by amino acid signaling through intercellular crosstalk between pancreatic endocrine cells

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K08547
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54040:Metabolism and endocrinology-related
• Research Institution: Gunma University
• Principal Investigator: Nakagawa Yuko 群馬大学, 生体調節研究所, 助教 (90422500)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: PP細胞 / グルカゴン

Outline of Final Research Achievements

In vivo, each organ strictly controls the quantity and fate of cells to maintain normal function. In the pancreatic islets, which are endocrine cells of the pancreas, the quantities of the four types of cells-α, β, δ, and PP-are each precisely regulated. The breakdown of control over cell proliferation and fate maintenance directly leads to the onset of diseases such as diabetes. PP cells constitute only a small percentage of the pancreatic islet endocrine cells, and their function is mostly unexplored. This study discovered that the proliferation of PP cells is regulated by amino acid signals controlled by glucagon. These results suggest that amino acid signaling may play a crucial role in maintaining the fate of pancreatic islet cells by controlling their plasticity.

Free Research Field

生理学

Academic Significance and Societal Importance of the Research Achievements

膵内分泌細胞のPP細胞についての報告は少なく、特にその生理的機能については、殆ど未開拓であった。私達はPP細胞またPP細胞より分泌するPPの機能解析に必要なリソースを揃え、精力的にPP細胞の生理的機能について解析を進めてきた。本研究では、PP細胞の増殖と可塑性をグルカゴンが制御していることを見出した。近年、血中のアミノ酸濃度バランスが変化することによりがん細胞の悪性度を促進させることが報告されているが、本研究では正常な膵内分泌細胞がアミノ酸濃度の変化により増殖が劇的に亢進し、多重ホルモン発現細胞を誘導することを見出した。本研究の成果は極めて新規性高い発見に繋がることが考えられる。