Investigation of the multifaceted roles of nardilysin in homeostatic maintenance

2016 Fiscal Year Final Research Report

• Project/Area Number: 26293068
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Pathological medical chemistry
• Research Institution: Kyoto University
• Principal Investigator: NIshi Eiichiro 京都大学, 医学(系)研究科(研究院), 講師 (30362528)
• Co-Investigator(Kenkyū-buntansha): 大野 美紀子 京都大学, 医学(系)研究科(研究院), 助教 (10583198)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 恒常性

Outline of Final Research Achievements

Homeostasis is the property that living things use to actively maintain fairly stable conditions necessary for survival. Molecular mechanism by which the set point of homeostatic regulation is determined has not been clarified. Nardilysin (NRDC)-deficient mice show hypothermia, bradycardia and hypoinsulinemia, in which “normal” negative feedback system appears not to work. These findings suggest that NRDC plays important roles in the determination of homeostatic set points. Here, we demonstrate that NRDC-deficient mice showed glucose intolerance and severely decreased glucose-stimulated insulin secretion (GSIS). Moreover, beta-cell-specific NRDC-deficient mice showed a diabetic phenotype with markedly reduced GSIS. ChIP assay revealed that NRDC is associated with Islet-1 in the enhancer region of MafA, where NRDC controls the recruitment of Islet-1 and MafA transcription. Our findings demonstrate that NRDC controls beta-cell function via regulation of the Islet-1-MafA pathway.

Free Research Field

分子病態医化学