期刊
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
卷 310, 期 1, 页码 E91-E102出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpendo.00285.2015
关键词
diabetes; transcription factor; nonhuman primate; islet; alpha-cell
资金
- National Institutes of Health [RO1-DK-090570, DK-66636, DK-68854, DK-72473, DK-89572, DK-089538, T32-DK-007563, R24-DK-093437, P51-OD-0110921]
- Vanderbilt Diabetes Research and Training Center [DK-20593]
- Veterans Affairs Research Service [BX000666]
- March of Dimes [1-FY08-381]
- Juvenile Diabetes Research Foundation (JDRF) [26-2008-863]
- Vanderbilt University Medical Center Cell Imaging Shared Resource [DK-20593, CA-68485, DK-58404, HD-15052, DK-59637, EY-08126]
- Vanderbilt University Medical Center Islet Procurement and Analysis Core [DK-20593]
- National Institute of Diabetes and Digestive and Kidney Diseases
Analysis of MafB(-/-) mice has suggested that the MAFB transcription factor was essential to islet alpha- and beta-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(Delta panc)) and MafA/B (MafAB(Delta panc)) with deficiencies associated with the related beta-cell-enriched MafA mutant (MafA(Delta panc)). Insulin(+) cell production and beta-cell activity were merely delayed in MafB(Delta panc) islets until MafA was comprehensively expressed in this cell population. We propose that MafA compensates for the absence of MafB in MafB(Delta panc) mice, which is supported by the death of MafAB(Delta panc) mice soon after birth from hyperglycemia. However, glucose-induced glucagon secretion was compromised in adult MafB(Delta panc) islet alpha-cells. Based upon these results, we conclude that MafB is only essential to islet alpha-cell activity and not beta-cell. Interestingly, a notable difference between mice and humans is that MAFB is coexpressed with MAFA in adult human islet beta-cells. Here, we show that nonhuman primate (NHP) islet alpha- and beta-cells also produce MAFB, implying that MAFB represents a unique signature and likely important regulator of the primate islet beta-cell.
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