3 years ago

MafB is critical for glucagon production and secretion in mouse pancreatic α-cells in vivo.

Hisashi Oishi, Satoru Takahashi, Megumi C Katoh, Walaa A Basha, Chioma M Ugbama, Miki Shimbo, Yunshin Jung, Takashi Kudo, Akihiro Kuno
The MafB transcription factor is expressed in pancreatic α- and β-cells during development but becomes exclusive to α-cells in adult rodents. Mafb-null (Mafb-/- ) mice were reported to reduce α- and β-cell numbers throughout embryonic development. To further analyze postnatal function of MafB in the pancreas, we generated endocrine cell-specific (MafbΔEndo ) and tamoxifen-dependent (MafbΔTAM ) Mafb knockout mice. MafbΔEndo mice exhibited reduced population of insulin+ and glucagon+ cells at postnatal day 0 but recovered the insulin+ cell population by 8 weeks of age. In contrast, Arx+/glucagon+ cell fraction and glucagon expression remained decreased even in adulthood. MafbΔTAM mice, with Mafb deleted after pancreas maturation, also demonstrated diminished glucagon+ cells and glucagon content without affecting β-cells. Decreased Arx+/glucagon+ cell population in MafbΔEndo mice was compensated by increased Arx+/pancreatic polypeptide+ cell population. Furthermore, gene expression analyses from both MafbΔEndo and MafbΔTAM islets revealed that MafB is a key regulator of glucagon expression in α-cells. Finally, both mutants failed to respond to arginine, likely due to impaired arginine transporter gene expression and glucagon production ability. Taken together, our findings reveal that MafB is critical for the functional maintenance of mouse α-cells in vivo, including glucagon production and secretion, as well as in development.

Publisher URL: http://doi.org/10.1128/MCB.00504-17

DOI: 10.1128/MCB.00504-17

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