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

Conrad E, Dai C, Spaeth J, Guo M, Cyphert HA, Scoville D, Carroll J, Yu WM, Goodrich LV, Harlan DM, Grove KL, Roberts CT, Powers AC, Gu G, Stein R
Am J Physiol Endocrinol Metab. 2016 310 (1): E91-E102

PMID: 26554594 · PMCID: PMC4675799 · DOI:10.1152/ajpendo.00285.2015

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 (MafB(Δpanc)) and MafA/B (MafAB(Δpanc)) with deficiencies associated with the related β-cell-enriched MafA mutant (MafA(Δpanc)). Insulin(+) cell production and β-cell activity were merely delayed in MafB(Δpanc) islets until MafA was comprehensively expressed in this cell population. We propose that MafA compensates for the absence of MafB in MafB(Δpanc) mice, which is supported by the death of MafAB(Δpanc) mice soon after birth from hyperglycemia. However, glucose-induced glucagon secretion was compromised in adult MafB(Δpanc) 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.

MeSH Terms (18)

Adolescent Adult Animals Biomarkers Female Humans Insulin-Secreting Cells Islets of Langerhans Macaca mulatta MafB Transcription Factor Male Mice Mice, Inbred C57BL Mice, Knockout Middle Aged Primates Rodentia Young Adult

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