Elucidation of PPY cell lineage for development of new diabetes treatment

2014 Fiscal Year Final Research Report

• Project/Area Number: 25860757
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Metabolomics
• Research Institution: Juntendo University
• Principal Investigator: HARA Akemi 順天堂大学, 医学部, 博士研究員 (60570009)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: PPY細胞 / β細胞 / 分化転換 / 細胞系譜 / 糖尿病 / 高血糖

Outline of Final Research Achievements

Persistent hyperglycemia with obese results in reduced pancreatic beta cell function and mass, and increased pancreatic polypeptide (PP) cells. The aim of this study was to elucidate the mechanism of the fate conversion between beta and PP cells, using lineage traceable mice, which were given high fat diet and STZ. The increased PP cells were found to originate from the pre-existing beta cells. The expression of a-beta cell specific transcription factor, Pdx1 was downregulated. By the knockdown of Pdx1 in MIN6 cells induced increment of PP mRNA expression. These results demonstrate the possibility that persistent hyperglycemia can induce beta to PP cell fate conversion in adult pancreas by the attenuation of Pdx1.
Furthermore, we found evidence that Some beta cells were originated from pre-existing PP cells during development. Hence, we are investigating the mechanisms underlying the reciprocal fate conversion between PP and beta cell lineages in pathophysiological conditions.

Free Research Field

細胞生物学