The MafA transcription factor becomes essential to islet β-cells soon after birth

Yan Hang, Tsunehiko Yamamoto, Richard K.P. Benninger, Marcela Brissova, Min Guo, Will Bush, David W. Piston, Alvin C. Powers, Mark Magnuson, Debbie C. Thurmond, Roland Stein

Research output: Contribution to journalArticle

60 Scopus citations

Abstract

The large Maf transcription factors, MafA and MafB, are expressed with distinct spatial+temporal patterns in rodent islet cells. Analysis of Mafa2/2 and pancreasspecific Mafaδpanc deletion mutant mice demonstrated a primary role for MafA in adult β-cell activity, different from the embryonic importance of MafB. Our interests here were to precisely define when MafA became functionally significant to β-cell, to determine how this was affected by the brief period of postnatal MafB production, and to identify genes regulated by MafA during this period. We found that islet cell organization, β-cell mass, and β-cell function were influenced by 3 weeks of age in MafaDpanc mice and compromised earlier in Mafa δpanc;Mafb+/- mice. A combination of genome-wide microarray profiling, electron microscopy, and metabolic assays were used to reveal mechanisms of MafA control. For example, β-cell replication was produced by actions on cyclin D2 regulation, while effects on granule docking affected first-phase insulin secretion. Moreover, notable differences in the genes regulated by embryonic MafB and postnatal MafA gene expression were found. These results not only clearly define why MafA is an essential transcriptional regulator of islet β-cell, but also why cell maturation involves coordinated actions with MafB.

Original languageEnglish (US)
Pages (from-to)1994-2005
Number of pages12
JournalDiabetes
Volume63
Issue number6
DOIs
StatePublished - Jun 2014

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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    Hang, Y., Yamamoto, T., Benninger, R. K. P., Brissova, M., Guo, M., Bush, W., Piston, D. W., Powers, A. C., Magnuson, M., Thurmond, D. C., & Stein, R. (2014). The MafA transcription factor becomes essential to islet β-cells soon after birth. Diabetes, 63(6), 1994-2005. https://doi.org/10.2337/db13-1001