Study of regulation on the function of male reproduction by incretin using model animals of obesity and diabetes

Research Project

Project/Area Number	18K06033
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 42040:Laboratory animal science-related
Research Institution	Kagoshima University
Principal Investigator	Asano Atsushi 鹿児島大学, 農水産獣医学域獣医学系, 教授 (90312404)
Project Period (FY)	2018-04-01 – 2021-03-31
Project Status	Completed (Fiscal Year 2020)
Budget Amount *help	¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000) Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000) Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000) Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords	マウス / インクレチン / 精子形成 / 精巣
Outline of Final Research Achievements	In the testes of mice, incretin receptors and incretin expression were observed. Incretin stimulation transiently enhanced the expression of cytokine-related genes and steroid synthesis-related genes in TM4 (Sertoli cell line) or MA-10 (Leydig cell line), Furthermore, in TM4 and MA-10, activation of cAMP-mediated signaling pathway was observed after incretin stimulation. In addition, the same induction of gene expression seen in TM4 was observed in C57BL/6J mice treated with GLP-1 receptor agonist (exenatide). These results indicate that incretins are responsible for the regulation of spermatogenesis-related gene expression.
Academic Significance and Societal Importance of the Research Achievements	インクレチンは精巣内の細胞に作用して、精子形成に関連する遺伝子の発現を正に制御することが示された。また、肥満や糖尿病の病態は精巣に対するインクレチンの作用、特にGIPの作用に影響を与える可能性が示唆された。今後、引き続き肥満・糖尿病モデル動物を利用し、雄性生殖機能に対するインクレチンの作用機序を解析することによって、エネルギー代謝調節異常と生殖機能低下症との関連性の解明につながることが期待される。