Investigation of the role of pancreatic alpha cells in relationship between bone and systemic metabolism.

2020 Fiscal Year Final Research Report

• Project/Area Number: 17K11649
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Functional basic dentistry
• Research Institution: Kyushu Dental College
• Principal Investigator: Takeuchi Hiroshi 九州歯科大学, 歯学部, 教授 (70304813)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Keywords: メタボリックシンドローム / 骨代謝 / 糖代謝 / オステオカルシン / インクレチン / GLP-1 / 膵α細胞

Outline of Final Research Achievements

Continuous administration of the bone-derived osteocalcin (OC) resulted in increased GLP-1-producing cells in the pancreatic island in mice. Using acutely isolated mouse pancreatic islets and cultured α cells, we identified that OC directly acted on the receptor GPRC6A in pancreatic α cells to activate the cAMP pathway leading to the expression of the transcription factor Pax6. Then it was followed by promoting the expression of PC1/3 which converts proglucagon to GLP-1 instead of glucagon, and suppressing the expression of Pcsk1n that is an inhibitor of PC1/3 enzymatic activity. Thus, OC directly acts on the pancreatic α cells and induces switching its producing hormones.

Free Research Field

歯科基礎医学

Academic Significance and Societal Importance of the Research Achievements

本研究では、骨基質タンパク質オステオカルシンによる全身の糖・エネルギー代謝改善効果の新たな作用機序を解明した。オステオカルシンに、血糖値を上昇させるグルカゴンから血糖値を下げる働きを補助する GLP-1 へと膵α細胞が産生するホルモンをスイッチさせる働きがあることを見出して、その作用機構の一端を明らかにした本研究の成果は学術的に意義深い。また、生活習慣病に対する新たな予防・治療戦略の開発に寄与する可能性がある。