| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2015: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2013: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
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| Outline of Final Research Achievements |
To analyze newly-generated β cells with better time resolution, we developed the reporter mouse models“Insulin-Timer", which permitted sequential analyses of the sorted endocrine progenitors and revealed their unique features [Miyatsuka et al. Diabetes 63: 3388-3393, 2014]. Furthermore, microarray analysis identified genes specifically expressed in endocrine progenitors during development. Among these genes, we focused on GLP-1 receptor (Glp1r), which plays an essential role in acinar-to-β reprogramming and generated the transgenic mouse model "exo-Glp1r", which expressed Glp1r exclusively in exocrine cells. When exo-Glp1r mice were treated with the GLP-1 analogs exendin-4 and gastrin, a fraction of the exocrine cells were reprogrammed into insulin-producing cells. The exocrine-derived β cells formed islet-like clusters in the pancreata of exo-Glp1r mice. These findings propose possible directions of future therapies for generating β cells via these signaling pathways.
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