The role of calcium-sensing receptors in the regulation of pancreatic beta cell and intestinal epithelial cell function.

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K16234
• 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: The University of Tokushima
• Principal Investigator: KURAHASHI Kiyoe 徳島大学, 大学院医歯薬学研究部(医学域), 助教 (30567342)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: 糖尿病 / 膵β細胞 / カルシウム感知受容体 / Calcilytic

Outline of Final Research Achievements

Human active mutant CaSR knock-in mice (ADH-KI) showed abnormal glucose tolerance with decreased insulin secretion, but the insulin content per islet and the number of islets were not different from those of wild-type mice, suggesting that the mechanism of decreased insulin secretion due to constant activation of CaSR signaling was not a decrease in pancreatic beta cell volume, but a decrease in insulin secretion. ADH-KI was administered with an inhibitor of CaSR, which had trend of improving glucose tolerance, suggesting that CaSR may be a novel target for drug therapy for diabetes.

Free Research Field

糖尿病

Academic Significance and Societal Importance of the Research Achievements

既報では活性型変異CaSRによる耐糖能異常は膵β細胞量の減少によるとされていたが、本研究では新たな機序として膵β細胞のインスリン分泌機構の異常を見出した。CaSR阻害薬の投与によりインスリン分泌の改善が認められたことから、CaSRが糖尿病の治療標的となりうることを見出した。CaSRを標的とした糖尿病治療は類を見ず、画期的と考えられる。今後、膵β細胞選択的なヒト活性型変異CaSRノックインマウスを作出するなどしてさらに機序の解明を進め、CaSRを新たな治療標的として確立していく。