Regulatory mechanisms of human beta cell mass and its association with glucose tolerance

• Project/Area Number: 18K08488
• 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: Keio University
• Principal Investigator: SAISHO YOSHIFUMI 慶應義塾大学, 医学部(信濃町), 講師 (90327510)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: β細胞量 / 2型糖尿病 / 耐糖能異常 / β細胞機能 / α細胞量 / 組織学的検討 / 膵β細胞 / インスリン / グルカゴン / 肥満 / 低出生体重 / 膵β細胞量 / 膵α細胞量 / ヒト膵組織 / 免疫染色 / 糖尿病 / 内分泌細胞 / ヒト / 膵組織 / 日本人

Outline of Final Research Achievements

Using histological analysis of human pancreas obtained from autopsy or pancreatic surgery, we found that in Japanese, 1) beta cell mass is already reduced in individuals with prediabetes before the onset of type 2 diabetes, and 2) birthweight is positively associated with beta cell mass in adults, indicating the possibility that reduced beta cell mass in individuals born with low birthweight increases a risk of developing type 2 diabetes in adulthood.

Academic Significance and Societal Importance of the Research Achievements

2型糖尿病は世界中で増加の一途をたどっており、その予防および新たな治療法の開発は喫緊の課題である。我々は、2型糖尿病患者におけるβ細胞量の減少を報告し、糖尿病の予防や治療における「β細胞保護」の重要性を提唱してきた。本検討では糖尿病を発症する以前の「糖尿病予備群」の段階においてすでにβ細胞量は減少し始めていることを明らかとし、より早期からの「β細胞保護」を目指した治療介入が糖尿病発症予防に重要であることを示した。また、出生体重がβ細胞量と関連することを明らかとし、将来の糖尿病発症予防の観点から低出生体重を回避する重要性を示した。

Research Products

• [Journal Article] Reduced beta cell number rather than size is a major contributor to beta cell loss in type 2 diabetes (2021)
  • Author(s): Sasaki Hironobu, Saisho Yoshifumi et al.
  • Journal Title: Diabetologia Volume: 印刷中
  • Peer Reviewed / Open Access
• [Journal Article] An emerging new concept for the management of type 2 diabetes with a paradigm shift from the glucose-centric to beta cell-centric concept of diabetes - an Asian perspective (2020)
  • Author(s): Saisho Yoshifumi
  • Journal Title: Expert Opinion on Pharmacotherapy Volume: 21 Issue: 13 Pages: 1565-1578
  • DOI: 10.1080/14656566.2020.1776262
  • Peer Reviewed / Open Access
• [Journal Article] Beta-Cell Mass in Obesity and Type 2 Diabetes, and Its Relation to Pancreas Fat: A Mini-Review (2020)
  • Author(s): Inaishi Jun、Saisho Yoshifumi
  • Journal Title: Nutrients Volume: 12 Issue: 12 Pages: 3846-3846
  • DOI: 10.3390/nu12123846
  • Peer Reviewed / Open Access
• [Journal Article] Association of glucose tolerance status with pancreatic β‐ and α‐cell mass in community‐based autopsy samples of Japanese individuals: The Hisayama Study (2020)
  • Author(s): Inaishi Jun、Saisho Yoshifumi、Hirakawa Yoichiro、Yoshida Daigo、Hata Jun、Mukai Naoko、Watanabe Yuusuke、Oda Yoshinao、Itoh Hiroshi、Ninomiya Toshiharu
  • Journal Title: Journal of Diabetes Investigation Volume: - Issue: 5 Pages: 1197-1206
  • DOI: 10.1111/jdi.13232
  • Peer Reviewed / Open Access
• [Journal Article] Associations of birthweight and history of childhood obesity with beta cell mass in Japanese adults (2020)
  • Author(s): Sasaki H, Saisho Y, Inaishi J, Watanabe Y, Tsuchiya T, Makio M, Sato M, Kitago M, Yamada T, Itoh H
  • Journal Title: Diabetologia Volume: - Issue: 6 Pages: 1199-1210
  • DOI: 10.1007/s00125-020-05127-2
  • Peer Reviewed / Open Access
• [Journal Article] Comprehensive study on human pancreatic beta-cell regulatory mechanism (2019)
  • Author(s): Yoshifumi Saisho
  • Journal Title: Impact Volume: na Issue: 2 Pages: 38-40
  • DOI: 10.21820/23987073.2019.2.38
  • Open Access / Int'l Joint Research
• [Journal Article] Changing the Concept of Type 2 Diabetes: Beta Cell Workload Hypothesis Revisited (2019)
  • Author(s): Yoshifumi Saisho
  • Journal Title: Endocrine, metabolic & immune disorders drug targets Volume: 19 Issue: 2 Pages: 121-127
  • DOI: 10.2174/1871530318666180821161825
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] How can we develop more effective strategies for type 2 diabetes mellitus prevention? A paradigm shift from a glucose-centric to a beta cell-centric concept of diabetes (2018)
  • Author(s): Yoshifumi Saisho
  • Journal Title: European Medical Journal Diabetes Volume: 6 Pages: 46-52
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] 剖検例における耐糖能と膵β・α細胞量に関する検討 久山町研究 (2020)
  • Author(s): 稲石淳, 税所芳史, 平川洋一郎, 吉田大悟, 秦淳, 向井直子, 渡辺雄祐, 小田義直, 伊藤裕, 二宮利治
  • Organizer: 日本内科学会
• [Presentation] ヒト膵摘出症例における出生体重とα・β細胞量の関係についての検討 (2020)
  • Author(s): 佐々木 裕伸,税所 芳史,稲石 淳,渡辺 雄祐,土屋 多美,牧尾 将幹,佐藤 翠,北郷 実,北川 雄光,山田 健 人,伊藤 裕
  • Organizer: 日本糖尿病学会
• [Presentation] Glucose tolerance status and beta and alpha cellmass in community-based autopsy samples of Japanese: the Hisayama study (2019)
  • Author(s): Inaishi J, Saisho Y, Mukai N, Hirakawa Y, Yoshida D, Hata J, Watanabe Y, Oda Y, Itoh H, Ninomiya T
  • Organizer: 55th Annual Meeting of the European Association for the Study of Diabetes
• [Presentation] Effects of obesity and diabetes on pancreatic endocrine cell mass and the relative change in humans (2019)
  • Author(s): Watanabe Y, Saisho Y, Inaishi J, Murakami R, Tsuchiya T, Sasaki H, Makio M, Kitago M, Kitagawa Y, Yamada T, Itoh H
  • Organizer: 55th Annual Meeting of the European Association for the Study of Diabetes
• [Presentation] 肥満,糖尿病におけるヒト膵内分泌細胞量の変化についての検討 (2019)
  • Author(s): 渡辺雄祐, 税所芳史, 稲石淳, 村上理恵, 土屋多美, 佐々木裕伸, 牧尾将幹, 北郷実, 北川雄光, 山田健人, 伊藤裕
  • Organizer: 第62回日本糖尿病学会年次学術集会
• [Presentation] 久山町剖検例における糖代謝関連因子および遺伝的背景とα・β細胞量との関連 (2019)
  • Author(s): 稲石淳, 税所芳史, 向井直子, 平川洋一郎, 吉田大悟, 秦淳, 渡辺雄祐, 小田義直, 伊藤裕, 二宮利治
  • Organizer: 第62回日本糖尿病学会年次学術集会
• [Presentation] 日本人での耐糖能とβ細胞機能および膵組織学的特徴との関連についての検討 (2019)
  • Author(s): 稲石淳, 税所芳史, 向井直子, 平川洋一郎, 吉田大悟, 秦淳, 渡辺雄祐, 小田義直, 伊藤裕, 二宮利治
  • Organizer: 第62回日本糖尿病学会年次学術集会
• [Presentation] 久山町剖検例における糖代謝関連因子とα・β細胞量との関連 (2018)
  • Author(s): 稲石淳, 税所芳史, 向井直子, 平川洋一郎, 吉田大悟, 秦淳, 渡辺雄祐, 小田義直, 伊藤裕, 二宮利治
  • Organizer: 第61回日本糖尿病学会年次学術集会
• [Presentation] 肥満、糖尿病におけるヒト膵内分泌細胞量の変化についての検討 (2018)
  • Author(s): 渡辺雄祐, 税所芳史, 稲石淳, 村上理恵, 土屋多美, 佐々木裕伸, 北郷実, 北川雄光, 山田健人, 伊藤裕
  • Organizer: 第61回日本糖尿病学会年次学術集会