title: The MAFB transcription factor impacts islet α-cell function in rodents and represents a unique signature of primate islet β-cells.
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.
authors.affiliation: Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, Nashville, Tennessee;
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Conrad
authors.affiliation: Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee;
authors.forename: Chunhua
authors.initials: C
authors.lastname: Dai
authors.affiliation: Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, Nashville, Tennessee;
authors.forename: Jason
authors.initials: J
authors.lastname: Spaeth
authors.affiliation: Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, Nashville, Tennessee;
authors.forename: Min
authors.initials: M
authors.lastname: Guo
authors.affiliation: Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, Nashville, Tennessee;
authors.forename: Holly A
authors.initials: HA
authors.lastname: Cyphert
authors.affiliation: Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, Nashville, Tennessee;
authors.forename: David
authors.initials: D
authors.lastname: Scoville
authors.affiliation: Division of Diabetes, Obesity, and Metabolism, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, Oregon;
authors.forename: Julie
authors.initials: J
authors.lastname: Carroll
authors.affiliation: Department of Neurobiology, Harvard Medical School, Boston, Massachusetts;
authors.forename: Wei-Ming
authors.initials: WM
authors.lastname: Yu
authors.affiliation: Department of Neurobiology, Harvard Medical School, Boston, Massachusetts;
authors.forename: Lisa V
authors.initials: LV
authors.lastname: Goodrich
authors.affiliation: Department of Medicine, University of Massachusetts, Worcester, Massachusetts;
authors.forename: David M
authors.initials: DM
authors.lastname: Harlan
authors.affiliation: Division of Diabetes, Obesity, and Metabolism, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, Oregon;
authors.forename: Kevin L
authors.initials: KL
authors.lastname: Grove
authors.affiliation: Division of Diabetes, Obesity, and Metabolism, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, Oregon;
authors.forename: Charles T
authors.initials: CT
authors.lastname: Roberts
authors.affiliation: 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.
authors.forename: Alvin C
authors.initials: AC
authors.lastname: Powers
authors.affiliation: Department of Cell and Developmental Biology, Vanderbilt University Medical Center, Nashville, Tennessee.
authors.forename: Guoqiang
authors.initials: G
authors.lastname: Gu
authors.affiliation: Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, Nashville, Tennessee; roland.stein@vanderbilt.edu.
authors.forename: Roland
authors.initials: R
authors.lastname: Stein
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D005260:Female; D006801:Humans; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D007515:Islets of Langerhans / Q000502:physiology*; D008253:Macaca mulatta; D051258:MafB Transcription Factor / Q000235:genetics / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008875:Middle Aged; D011323:Primates; D012377:Rodentia; D055815:Young Adult
chemical_list: D015415:Biomarkers; C490407:MAFB protein, human; D051258:MafB Transcription Factor
keywords: diabetes; islet; nonhuman primate; transcription factor; α-cell