Investigation of the function of STIM in pancreatic b-cells

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K23966
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0902:General internal medicine and related fields
• Research Institution: Kyoto University
• Principal Investigator: USUI RYOTA 京都大学, 医学研究科, 特定助教 (40850996)
• Project Period (FY): 2019-08-30 – 2021-03-31
• Keywords: インスリン分泌 / カルシウム

Outline of Final Research Achievements

Store-operated Ca2+ entry (SOCE) is activated by endoplasmic reticulum (ER) Ca2+ sensor STIM1 which senses depletion of Ca2+ from the ER, and induces extracellular Ca2+ influx through Orai1 to the cytosol to maintain intracellular Ca2+ homeostasis in various cell types, however the role of SOCE in pancreatic b-cells remains largely unknown.
STIM1 or Orai1 KD MIN6 cells and islets from b-cell-specific STIM1 KO mice similarly abolished GPR40 agonist, fas-mediated potentiation of GIIS and fas-induced elevation of intracellular Ca2+ levels, while there was little effect on GIIS itself. In OGTT, blood glucose levels were similar in control mice and STIM1 KO mice without fas administration, however fas-mediated glucose lowering and insulin increasing effect were significantly lower compared with control. GPR40 signal activates STIM1 and SOCE activated by STIM1 is essential for GPR40-mediated potentiation of GIIS.

Free Research Field

インスリン分泌

Academic Significance and Societal Importance of the Research Achievements

膵β細胞にはグルコース応答性インスリン分泌以外にも様々なインスリン分泌調整機構が存在しているが、栄養素の一つである脂肪酸刺激によるインスリン分泌増強作用において、今回新たにSTIM1という因子が重要な役割を担っていることを明らかにした。
糖尿病患者においては膵β細胞のSTIM1発現量が低下しているという報告もあり、本研究における成果とあわせて栄養素、あるいは糖尿病治療薬の効果予測因子としてSTIM1が有用である可能性を示唆した。