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Am J Physiol Endocrinol Metab. 2016 Jan 1;310(1):E91-E102. doi: 10.1152/ajpendo.00285.2015. Epub 2015 Nov 10.

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

Author information

1
Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, Nashville, Tennessee;
2
Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee;
3
Division of Diabetes, Obesity, and Metabolism, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, Oregon;
4
Department of Neurobiology, Harvard Medical School, Boston, Massachusetts;
5
Department of Medicine, University of Massachusetts, Worcester, Massachusetts;
6
Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, Nashville, Tennessee; Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee; Veterans Affairs Tennessee Valley Healthcare System, Nashville, Tennessee; and.
7
Department of Cell and Developmental Biology, Vanderbilt University Medical Center, Nashville, Tennessee.
8
Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, Nashville, Tennessee; roland.stein@vanderbilt.edu.

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 (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.

KEYWORDS:

diabetes; islet; nonhuman primate; transcription factor; α-cell

PMID:
26554594
PMCID:
PMC4675799
DOI:
10.1152/ajpendo.00285.2015
[Indexed for MEDLINE]
Free PMC Article

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