Regulation of insulin secretion by carbonic anhydrase 8 (Car8) in pancreatic beta cells

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K17489
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 54040:Metabolism and endocrinology-related
• Research Institution: Kyoto University
• Principal Investigator: Usui Ryota 京都大学, 医学研究科, 客員研究員 (40850996)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: カルシウム / 糖新生 / インスリン分泌

Outline of Final Research Achievements

There was no significant differences in insulin secretion or intracellular calcium between isolated islets from Car8-deficient mice and wild-type mice. This may be due to the low expression of Car8 in isolated islets.
On the other hand, Car8 is highly expressed in hepatocytes, then glycogenesis was significantly increased in hepatocytes isolated from Car8 knockout mice compared to wild-type mice. Intracellular calcium concentration in the presence of glycosylation-inducing substrates such as pyruvate and lactate was also significantly increased in the hepatocytes from Car8 knockout mice compared to wild-type mice.
This suggests that Car8 negatively regulates glycogenesis via intracellular calcium signaling.

Free Research Field

インスリン分泌

Academic Significance and Societal Importance of the Research Achievements

糖代謝において、膵β細胞によるインスリン分泌のみならず、肝臓での糖新生も需要な役割を担っている。
今回単離膵島、及び膵β細胞株においては発現量の少ないことが影響してかCar8欠損によるインスリン分泌の変化は同定できなかったが、肝細胞においてはCar8は細胞内カルシウムシグナルを介して糖新生を負に制御していることが示唆され、糖新生を制御する因子としてCar8がターゲットとなりえる可能性を示唆した。