title: Preserving Mafa expression in diabetic islet β-cells improves glycemic control in vivo.
abstract: The murine Mafa transcription factor is a key regulator of postnatal islet β-cell activity, affecting insulin transcription, insulin secretion, and β-cell mass. Human MAFA expression is also markedly decreased in islet β-cells of type 2 diabetes mellitus (T2DM) patients. Moreover, levels are profoundly reduced in db/db islet β-cells, a mouse model of T2DM. To examine the significance of this key islet β-cell-enriched protein to glycemic control under diabetic conditions, we generated transgenic mice that conditionally and specifically produced Mafa in db/db islet β-cells. Sustained expression of Mafa resulted in significantly lower plasma glucose levels, higher plasma insulin, and augmented islet β-cell mass. In addition, there was increased expression of insulin, Slc2a2, and newly identified Mafa-regulated genes involved in reducing β-cell stress, like Gsta1 and Gckr. Importantly, the levels of human GSTA1 were also compromised in T2DM islets. Collectively, these results illustrate how consequential the reduction in Mafa activity is to islet β-cell function under pathophysiological conditions.
authors: From the Department of Metabolic Medicine, matsuoka@endmet.med.osaka-u.ac.jp.
authors: Taka-aki
authors: TA
authors: Matsuoka
authors: From the Department of Metabolic Medicine.
authors: Hideaki
authors: H
authors: Kaneto
authors: From the Department of Metabolic Medicine.
authors: Satoshi
authors: S
authors: Kawashima
authors: From the Department of Metabolic Medicine.
authors: Takeshi
authors: T
authors: Miyatsuka
authors: From the Department of Metabolic Medicine.
authors: Yoshihiro
authors: Y
authors: Tochino
authors: From the Department of Metabolic Medicine.
authors: Atsushi
authors: A
authors: Yoshikawa
authors: From the Department of Metabolic Medicine.
authors: Akihisa
authors: A
authors: Imagawa
authors: the Division of Stem Cell Regulation Research, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors: Jun-ichi
authors: J
authors: Miyazaki
authors: the Department of Medicine, Division of Diabetes, Endocrinology, and Metabolism, Vanderbilt University Medical Center, Nashville, Tennessee 37232-6303, and.
authors: Maureen
authors: M
authors: Gannon
authors: the Department of Molecular Physiology & Biophysics, Vanderbilt University Medical School, Nashville, Tennessee 37232.
authors: Roland
authors: R
authors: Stein
authors: From the Department of Metabolic Medicine.
authors: Iichiro
authors: I
authors: Shimomura
mesh_terms: D000818:Animals; D001483:Base Sequence; D001786:Blood Glucose / Q000378:metabolism*; D017931:DNA Primers; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D006801:Humans; D007515:Islets of Langerhans / Q000378:metabolism*; D051473:Maf Transcription Factors, Large / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D001786:Blood Glucose; D017931:DNA Primers; D051473:Maf Transcription Factors, Large; C485160:Mafa protein, mouse
keywords: Diabetes; Glucose Metabolism; Insulin Synthesis; Insulin Transcription Factor; Islet; Mafa; Oxidative Stress
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