The MAFB transcription factor impacts islet α-cell function in rodents and represents a unique signature of primate islet β-cells

Elizabeth Conrad, Chunhua Dai, Jason Spaeth, Min Guo, Holly A. Cyphert, David Scoville, Julie Carroll, Wei Ming Yu, Lisa V. Goodrich, David M. Harlan, Kevin Grove, Charles Roberts, Alvin C. Powers, Guoqiang Gu, Roland Stein

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    13 Scopus citations

    Abstract

    Analysis of MafB−/−mice has suggested that the MAFB transcription factor was essential to islet α- and β-cell formation during development, although the postnatal physiological impact could not be studied here because these mutants died due to problems in neural development. Pancreas-wide mutant mice were generated to compare the postnatal significance of MafB (MafBΔpanc) and MafA/B (MafABΔpanc) with deficiencies associated with the related β-cell-enriched MafA mutant (MafAΔpanc). Insulin+ cell production and β-cell activity were merely delayed in MafBΔpanc islets until MafA was comprehensively expressed in this cell population. We propose that MafA compensates for the absence of MafB in MafBΔpanc mice, which is supported by the death of MafABΔpanc mice soon after birth from hyperglycemia. However, glucose-induced glucagon secretion was compromised in adult MafBΔpanc islet α-cells. Based upon these results, we conclude that MafB is only essential to islet α-cell activity and not β-cell. Interestingly, a notable difference between mice and humans is that MAFB is coexpressed with MAFA in adult human islet β-cells. Here, we show that nonhuman primate (NHP) islet α- and β-cells also produce MAFB, implying that MAFB represents a unique signature and likely important regulator of the primate islet β-cell.

    Original languageEnglish (US)
    Pages (from-to)E91-E102
    JournalAmerican Journal of Physiology - Endocrinology and Metabolism
    Volume310
    Issue number1
    DOIs
    StatePublished - 2015

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    Keywords

    • Diabetes
    • Islet
    • Nonhuman primate
    • Transcription factor
    • α-cell

    ASJC Scopus subject areas

    • Physiology
    • Physiology (medical)
    • Endocrinology, Diabetes and Metabolism

    Cite this

    Conrad, E., Dai, C., Spaeth, J., Guo, M., Cyphert, H. A., Scoville, D., Carroll, J., Yu, W. M., Goodrich, L. V., Harlan, D. M., Grove, K., Roberts, C., Powers, A. C., Gu, G., & Stein, R. (2015). The MAFB transcription factor impacts islet α-cell function in rodents and represents a unique signature of primate islet β-cells. American Journal of Physiology - Endocrinology and Metabolism, 310(1), E91-E102. https://doi.org/10.1152/ajpendo.00285.2015