| Budget Amount *help |
¥16,120,000 (Direct Cost: ¥12,400,000、Indirect Cost: ¥3,720,000)
Fiscal Year 2016: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2015: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2014: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
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| 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.
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