| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
|
|---|
| Outline of Final Research Achievements |
During progression of type 2 diabetes, pancreatic islet b-cells gradually lose their ability to secrete insulin in response to glucose. Loss or decrease of MafA transcription factor has been thought be responsible for the b-cell dysfunction. Here, we identified a intracellular system regulating MafA protein function and stability.
We found that an amino acid-related compound Taurine activates WNK kinase in b-cells, thereby maintains MafA protein levels. We also found that basal level autophagy is required for maintaining mafA mRNA transcription. Furthermore, glucocorticoid and related compounds inhibit ability of MafA-Beta2-HNF1b transcription factors to synergistically activate glut2 gene transcription. As Glut2 (glucose transporter 2) is an essential component of glucose-stimulated insulin secretion in b-cells, this mechanism may explain how steroids suppress b-cell function.
|
