Inhibition of Small Maf Function in Pancreatic β-Cells Improves Glucose Tolerance Through the Enhancement of Insulin Gene Transcription and Insulin Secretion

Endocrinology
Hiroshi NomotoTatsuya Atsumi

Abstract

The large-Maf transcription factor v-maf musculoaponeurotic fibrosarcoma oncogene homolog A (MafA) has been found to be crucial for insulin transcription and synthesis and for pancreatic β-cell function and maturation. However, insights about the effects of small Maf factors on β-cells are limited. Our goal was to elucidate the function of small-Maf factors on β-cells using an animal model of endogenous small-Maf dysfunction. Transgenic (Tg) mice with β-cell-specific expression of dominant-negative MafK (DN-MafK) experiments, which can suppress the function of all endogenous small-Mafs, were fed a high-fat diet, and their in vivo phenotypes were evaluated. Phenotypic analysis, glucose tolerance tests, morphologic examination of β-cells, and islet experiments were performed. DN-MafK-expressed MIN6 cells were also used for in vitro analysis. The results showed that DN-MafK expression inhibited endogenous small-Maf binding to insulin promoter while increasing MafA binding. DN-MafK Tg mice under high-fat diet conditions showed improved glucose metabolism compared with control mice via incremental insulin secretion, without causing changes in insulin sensitivity or MafA expression. Moreover, up-regulation of insulin and glucokinase ...Continue Reading

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Citations

Apr 9, 2016·Gene·Fumiki Katsuoka, Masayuki Yamamoto
Feb 24, 2016·PloS One·Ahmed M AbdellatifSatoru Takahashi
Nov 1, 2018·American Journal of Physiology. Renal Physiology·Masahiro OkabeTaiji Matsusaka
Jun 4, 2020·Nature Communications·Ronan RussellMatthias Hebrok
Jun 17, 2019·Metabolism: Clinical and Experimental·Kazuno OmoriTatsuya Atsumi

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