• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

The effect of insulin insufficiency and/or insulin resistance on pancreatic carcinogenesis and progression

Research Project

Project/Area Number 17K09461
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Gastroenterology
Research InstitutionOsaka University

Principal Investigator

Shigekawa Minoru  大阪大学, 医学系研究科, 助教 (00625436)

Co-Investigator(Kenkyū-buntansha) 小玉 尚宏  大阪大学, 医学系研究科, 助教 (10623275)
巽 智秀  大阪大学, 医学系研究科, 講師 (20397699)
疋田 隼人  大阪大学, 医学系研究科, 助教 (20623044)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords膵癌 / 糖尿病 / 高血糖状態 / 膵発癌 / 膵癌進展 / 膵前癌病変 / 動物モデル
Outline of Final Research Achievements

We focused on hyperglycemia and showed that hyperglycemia enhances pancreatic cancer progression. Streptozotocin-induced hyperglycemia in KrasLSL G12D Pdx1Cre (KP) mice promoted PanINs formation and progression. High-glucose environment showed increased cell viability and sphere formation in PANC-1, a Kras-mutant human pancreatic ductal cancer cell line, and mPKC1, a Kras-mutant murine pancreatic cancer cell line. STAT3 phosphorylation and MYC expression was elevated under high glucose environment in Kras-mutant cells. PanINs from diabetic KP mice showed stronger phosphorylated-STAT3 and MYC staining than those from euglycemic counterparts. STAT3 inhibition in Kras-mutant cell lines blocked the enhanced cell viability and sphere formation induced by the hyperglycemia, and reversed the elevated pSTAT3 and MYC expression. In conclusion, hyperglycemia, on a Kras-mutant background, aggravates the PanINs progression accompanied by elevated pSTAT3 and MYC expression.

Academic Significance and Societal Importance of the Research Achievements

糖尿病と膵癌の関係性のメカニズムは不明な点が多い。本研究では糖尿病の重要な側面の一つである高血糖に注目し、高血糖が膵発癌に与える影響について検討を行った。結果、高血糖はin vitro, in vivoの系において、STAT3のリン酸化とMYCの発現増強を伴って、膵発癌を進展させることが示唆された。厚生労働省の報告では、糖尿病を否定できない患者は国内でも1000万人程度存在するとされている。糖尿病患者の膵発癌をどう抑制するのか、また糖尿病患者の中からどう膵癌の高リスク群を選別するかが差し迫った課題である。本研究が解明した高血糖と膵癌の関係性はその一助となると考えている。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report

URL: 

Published: 2017-04-28   Modified: 2021-02-19  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi