Role of proglucagon positive cells in pathophysiology of diabetes.

2022 Fiscal Year Final Research Report

• Project/Area Number: 18K08498
• 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: Shiga University of Medical Science
• Principal Investigator: Fujita Yukihiro 滋賀医科大学, 医学部, 准教授 (20451461)
• Project Period (FY): 2018-04-01 – 2023-03-31
• Keywords: グルカゴン / GLP-1 / 膵α細胞 / 腸管内分泌細胞

Outline of Final Research Achievements

Alpha cells in the pancreatic islets and L cells, an enteroendocrine cells in the intestinal tract, identically express glucagon gene and a pro-hormone proglucagon. However differently from proglucagon, glucagon is released in the pancreatic alpha cells and GLP-1/GLP-2 is secreted in the intestinal tract. We have established a method to specifically collect proglucagon-positive cells using the transgenic mice in which glucagon gene-expressing cells fluoresce. We then investigated which hormones and transcription factors are expressed in proglucagon-positive cells in the gastrointestinal tract and the pancreas, and identified various factors that determine the induction of differentiation and functional expression of alpha cells and L cells. In addition, we have clarified how metabolic stress, such as high-fat diet, induces changes in these proglucagon-positive cells.

Free Research Field

糖尿病学、内分泌学

Academic Significance and Societal Importance of the Research Achievements

同じく膵臓から分泌されるインスリンに加えて、グルカゴンや消化管由来のGLP-1は糖尿病の発症や治療の領域で注目されている。同じ遺伝子から作られるグルカゴンとGLP-1がどのような機構でそれぞれ別のホルモンとして分泌されるがさらに解明されれば、糖尿病の新しい治療法の開発や病態の解明に役に立つことが期待される。