The MAFB transcription factor impacts islet a-cell function in rodents and represents a unique signature of primate islet (3-cells

摘要

Analysis of MafB~'- mice has suggested that the MAFB transcription factor was essential to islet a-and (3-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 {MafBApanc) and MafA/B (MafABApanc) with deficiencies associated with the related (3-cell-enriched MafA mutant (MafAApanc). Insulin"1" cell production and |3-cell activity were merely delayed in MafBApanc islets until MafA was comprehensively expressed in this cell population. We propose that MafA compensates for the absence of MafB in MafBApanc mice, which is supported by the death ofMafABApanc mice soon after birth from hyperglycemia. However, glucose-induced glu-cagon secretion was compromised in adult MafBApanc islet a-cells. Based upon these results, we conclude that MafB is only essential to islet a-cell activity and not P-cell. Interestingly, a notable difference between mice and humans is that MAFB is coexpressed with MAFA in adult human islet p-cells. Here, we show that nonhuman primate (NHP) islet a- and (3-cells also produce MAFB, implying that MAFB represents a unique signature and likely important regulator of the primate islet 3-cell.