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


: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 gene expression was observed both in vivo and in vitro under DN-MafK expression. We concluded that endogenous small-Maf factors negatively regulates β-cell function by competing for MafA binding, and thus, the inhibition of small-Maf activity can improve β-cell function.






Nomoto H,Kondo T,Miyoshi H,Nakamura A,Hida Y,Yamashita K,Sharma AJ,Atsumi T




Has Abstract


2015-10-01 00:00:00












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    abstract::Implantation of an embryo induces rapid proliferation and differentiation of uterine stromal cells, forming a new structure, the decidua. One salient feature of decidua formation is a marked increase in maternal angiogenesis. Vascular endothelial growth factor (VEGF)-dependent pathways are active in the ovary, uterus,...


    pub_type: 杂志文章


    authors: Douglas NC,Tang H,Gomez R,Pytowski B,Hicklin DJ,Sauer CM,Kitajewski J,Sauer MV,Zimmermann RC

    更新日期:2009-08-01 00:00:00

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    abstract::The induction of hepatic drug metabolizing enzymes alters not only the metabolism of the xenobiotic substances that induce them but also the metabolism of various endogenous hormones. The xenobiotic receptor constitutive androstane receptor (CAR) (NR1I3) mediates the well-studied induction of CYP2B genes and other dru...


    pub_type: 杂志文章


    authors: Qatanani M,Zhang J,Moore DD

    更新日期:2005-03-01 00:00:00

  • Insulin is present in chicken eggs and early chick embryos.

    abstract::We showed that insulin appears in the chick embryo before beta-cells are recognizable, as well as in the egg constituents even before fertilization. Acid-ethanol extracts of 2- to 8-day-old embryos were gel-filtered on Sephadex G-50. The peak of immunoreactive insulin chromatographed in a position corresponding to tha...


    pub_type: 杂志文章


    authors: De Pablo F,Roth J,Hernandez E,Pruss RM

    更新日期:1982-12-01 00:00:00

  • Differential expression of estrogen receptor-beta and estrogen receptor-alpha in the rat ovary.

    abstract::Immunohistochemical localization of two estrogen receptor (ER) subtypes, ER beta and ER alpha, was performed in neonatal, early postnatal, immature, and adult rats to determine whether ER alpha and ER beta are differentially expressed in the ovary. ER beta and ER alpha were visualized using a polyclonal anti-ER beta a...


    pub_type: 杂志文章


    authors: Sar M,Welsch F

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  • Hypokalemia decreases testosterone production in male mice by altering luteinizing hormone secretion.

    abstract::Potassium deficiency produced by feeding mice a low potassium diet caused a marked decrease in plasma and testicular testosterone concentrations and a concomitant fall in the weight of seminal vesicles and in renal ornithine decarboxylase activity. All of these parameters were rapidly restored when potassium supply wa...


    pub_type: 杂志文章


    authors: Sánchez-Capelo A,Castells MT,Cremades A,Peñafiel R

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  • Mechanisms involved in glucocorticoid induction of pituitary GH expression during embryonic development.

    abstract::Glucocorticoid hormones are involved in functional differentiation of GH-producing somatotrophs. Glucocorticoid treatment prematurely induces GH expression in mammals and birds in a process requiring protein synthesis and Rat sarcoma (Ras) signaling. The objective of this study was to investigate mechanisms through wh...


    pub_type: 杂志文章


    authors: Ellestad LE,Puckett SA,Porter TE

    更新日期:2015-03-01 00:00:00

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    pub_type: 杂志文章


    authors: Blackshear PJ,Nemenoff RA,Avruch J

    更新日期:1984-01-01 00:00:00

  • Pulsatility of immunoreactive somatomedin-C in chronically cannulated rats.

    abstract::Pituitary GH secretion is pulsatile in man and the rat, but evidence of pulsatility in the GH-dependent somatomedins (insulin-like growth factors) has not been described. In this study serum immunoreactive somatomedin-C periodicity was examined in 10 chronically cannulated unstressed rats. Blood samples were taken at ...


    pub_type: 杂志文章


    authors: Baxter RC,Zaltsman Z,Oliver JR,Willoughby JO

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  • Heparan sulfate proteoglycans regulate responses to oocyte paracrine signals in ovarian follicle morphogenesis.

    abstract::In the ovarian follicle, oocyte-secreted factors induce cumulus-specific genes and repress mural granulosa cell specific genes to establish these functionally distinct cell lineages. The mechanism establishing this precise morphogenic pattern of oocyte signaling within the follicle is unknown. The present study invest...


    pub_type: 杂志文章


    authors: Watson LN,Mottershead DG,Dunning KR,Robker RL,Gilchrist RB,Russell DL

    更新日期:2012-09-01 00:00:00

  • Effect of the antiestrogen ethamoxytriphetol (MER-25) and luteectomy on serum progesterone concentrations in pregnant baboons.

    abstract::The present study determined whether the reduction in serum progesterone (P4) concentrations which follows the administration of the antiestrogen ethamoxytriphetol [1-(rho-2-diethylaminoethoxyphenyl)1-phenyl-2-rho-methoxyphenyl ethanol (MER-25)] to pregnant baboons reflects a decline in placental and/or luteal functio...


    pub_type: 杂志文章


    authors: Albrecht ED,Pepe GJ

    更新日期:1984-11-01 00:00:00

  • Regulation of insulin-like growth factor I biosynthesis in porcine granulosa cells.

    abstract::In the present studies we examined the regulation of insulin-like growth factor I (IGF-I) expression in porcine granulosa cells in vitro. Using Northern analysis and ribonuclease protection assays with exon-specific probes, we identified the IGF-I messenger RNA (mRNA) transcripts present in these cells under basal and...


    pub_type: 杂志文章


    authors: Samaras SE,Canning SF,Barber JA,Simmen FA,Hammond JM

    更新日期:1996-11-01 00:00:00

  • Adenylate cyclase inhibition is not involved in the adrenal steroidogenic response to angiotensin II.

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    pub_type: 杂志文章


    authors: Woodcock EA,McLeod JK

    更新日期:1986-10-01 00:00:00

  • Characterization of specific glucocorticoid receptor in the Syrian hamster testis.

    abstract::Cytosols of whole testicular homogenates from the Syrian golden hamster contained specific binding sites for [3H]triamcinolone acetonide that exhibited limited capacity and high affinity binding characteristic of glucocorticoid receptors in other target tissues. The receptor complex sedimented as an 8.6S binder in low...


    pub_type: 杂志文章


    authors: Ortlip SA,Li SA,Li JJ

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  • Direct secretagogue effect of corticotropin-releasing factor on the rat adrenal cortex: the involvement of the zona medullaris.

    abstract::CRF dose-dependently enhanced corticosterone (B) secretion by rat adrenal slices including both cortex and medulla. Conversely, CRF did not exert any B response by fragments of adrenocortical autotransplants, which are completely deprived of chromaffin tissue. However, autotransplant quarters exhibited a dose-dependen...


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    authors: Andreis PG,Neri G,Mazzocchi G,Musajo F,Nussdorfer GG

    更新日期:1992-07-01 00:00:00

  • Osteoblasts mediate thyroid hormone stimulation of osteoclastic bone resorption.

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    pub_type: 杂志文章


    authors: Britto JM,Fenton AJ,Holloway WR,Nicholson GC

    更新日期:1994-01-01 00:00:00

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    abstract::Tumor necrosis factor-alpha (TNF) blocks LH-stimulated androstenedione production by immature rat theca-interstitial cells (TIC) in vitro. The mechanism for TNF inhibition of LH-induced androstenedione is unknown and was investigated. LH stimulation of androstenedione synthesis in TIC is mediated via a cAMP-dependent ...


    pub_type: 杂志文章


    authors: Zachow RJ,Tash JS,Terranova PF

    更新日期:1993-11-01 00:00:00

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    authors: Akeno N,Czyzyk-Krzeska MF,Gross TS,Clemens TL

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    pub_type: 杂志文章


    authors: Náray-Fejes-Tóth A,Rusvai E,Fejes-Tóth G

    更新日期:1994-04-01 00:00:00

  • Age-related changes in pulsatile luteinizing hormone release precede the transition to estrous acyclicity and depend upon estrous cycle history.

    abstract::Aging of the female reproductive system in rats is marked by discrete stages in the disappearance of regular estrous cyclicity. We determined at which point in the transition to acyclicity changes in the LH pulse generator could be detected by comparing pulsatile LH release in ovariectomized young rats to three groups...


    pub_type: 杂志文章


    authors: Scarbrough K,Wise PM

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  • Soluble ecto-domain mutant of thyrotropin (TSH) receptor incapable of binding TSH neutralizes the action of thyroid-stimulating antibodies from Graves' patients.

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    pub_type: 杂志文章


    authors: Osuga Y,Liang SG,Dallas JS,Wang C,Hsueh AJ

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  • Mechanisms of amylin/leptin synergy in rodent models.

    abstract::The present studies aimed to identify mechanisms contributing to amylin/leptin synergy in reducing body weight and adiposity. We reasoned that if amylin/leptin harnessed complementary neuronal pathways, then in the leptin-sensitive state, amylin should augment leptin signaling/binding and that in the absence of endoge...


    pub_type: 杂志文章


    authors: Turek VF,Trevaskis JL,Levin BE,Dunn-Meynell AA,Irani B,Gu G,Wittmer C,Griffin PS,Vu C,Parkes DG,Roth JD

    更新日期:2010-01-01 00:00:00

  • Ontogeny of the in vitro growth hormone stimulatory effect of thyrotropin-releasing hormone in the rat.

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    authors: Welsh JB,Cuttler L,Szabo M

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  • Hyperinsulinemia increases the amount of GLUT4 mRNA in white adipose tissue and decreases that of muscles: a clue for increased fat depot and insulin resistance.

    abstract::To mimick a state of hyperinsulinemia, normal rats were infused with insulin for 4 days via minipumps, and compared to saline infused rats. At the end of the experimental period, the abundance of mRNA was increased in white adipose tissue (WAT) and decreased in muscles of "insulinized" rats compared to controls. These...


    pub_type: 杂志文章


    authors: Cusin I,Terrettaz J,Rohner-Jeanrenaud F,Zarjevski N,Assimacopoulos-Jeannet F,Jeanrenaud B

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  • Expression of biologically active human thyrotropin (hTSH) in a baculovirus system: effect of insect cell glycosylation on hTSH activity in vitro and in vivo.

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    authors: Grossmann M,Wong R,Teh NG,Tropea JE,East-Palmer J,Weintraub BD,Szkudlinski MW

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    authors: Fujii E,Mellon SH

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    authors: Guzmán-Ruiz R,Somoza B,Gil-Ortega M,Merino B,Cano V,Attané C,Castan-Laurell I,Valet P,Fernández-Alfonso MS,Ruiz-Gayo M

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  • Regulation of androstenedione production by adenosine 3',5'-monophosphate and phorbol myristate acetate in ovarian thecal cells of the domestic hen.

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    pub_type: 杂志文章


    authors: Tilly JL,Johnson AL

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    pub_type: 杂志文章


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    pub_type: 杂志文章


    authors: Parrott JA,Skinner MK

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    pub_type: 杂志文章


    authors: Fink M,Acimovic J,Rezen T,Tansek N,Rozman D

    更新日期:2005-12-01 00:00:00