2020 Fiscal Year Final Research Report

Development of disease model in mice on the basis of mechanisms for pathogenesis of gestational diabetes.

Research Project

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Project/Area Number	18K19755
Research Category	Grant-in-Aid for Challenging Research (Exploratory)
Allocation Type	Multi-year Fund
Review Section	Medium-sized Section 59:Sports sciences, physical education, health sciences, and related fields
Research Institution	University of Shizuoka
Principal Investigator	Ishikawa Tomohisa 静岡県立大学, 薬学部, 教授 (10201914)
Co-Investigator(Kenkyū-buntansha)	金子雪子静岡県立大学, 薬学部, 講師 (00381038)
Project Period (FY)	2018-06-29 – 2021-03-31
Keywords	糖尿病 / β細胞 / メラトニン
Outline of Final Research Achievements	In mouse pancreatic islets, the expression of melatonin MT1 and MT2 receptors and AANAT, an enzyme that catalyzes production of N-acetylserotonin (NAS) from serotonin, was detected, although sexual differences were not observed in the levels of expression. The expression of HIOMT, an enzyme that catalyzes production of melatonin from NAS, was not detected in mouse pancreatic islets even in female gestation period. We also found that the expression of AANAT in pancreatic β cells was increased by the adenylate cyclase activator forskolin and that NAS suppresses glucose-stimulated insulin secretion (GSIS) via suppressing intracellular Ca2+ elevation. In summary, the results obtained here suggest that NAS is produced in pancreatic β cells in a cAMP-dependent manner and plays a role as a suppressor in GSIS; however, the evidence supporting the involvement of melatonin-related signaling in gestational diabetes has not been obtained.
Free Research Field	薬理学
Academic Significance and Societal Importance of the Research Achievements	末梢体内時計の同調因子として知られる松果体ホルモン・メラトニンは、主に松果体でセロトニンからAANATとHIOMTという２つの酵素を介して生成される。我々は、マウス膵島にAANATが発現していることを見出し、さらにセロトニンが妊娠中期に特異的に生成されることに着目して、膵β細胞におけるメラトニン関連シグナルが、発症機序が未だに不明な妊娠糖尿病と関連する可能性を考えた。残念ながら、メラトニン関連シグナルの妊娠糖尿病への関与を示す結果は得られなかったが、メラトニン産生の中途物質であるNASが膵β細胞で産生されてインスリン分泌調節に関与する可能性を示し、新たなインスリン分泌調節機構を提唱した。