Estrogens protect pancreatic beta-cells from apoptosis and prevent insulin-deficient diabetes mellitus in mice.

Abstract:

:In diabetes, the death of insulin-producing beta-cells by apoptosis leads to insulin deficiency. The lower prevalence of diabetes in females suggests that female sex steroids protect from beta-cell injury. Consistent with this hypothesis, 17beta-estradiol (estradiol) manifests antidiabetic actions in humans and rodents. In addition, estradiol has antiapoptotic actions in cells that are mediated by the estrogen receptor-a (ERalpha), raising the prospect that estradiol antidiabetic function may be due, in part, to a protection of beta-cell apoptosis via ERalpha. To address this question, we have used mice that were rendered estradiol-deficient or estradiol-resistant by targeted disruption of aromatase (ArKO) or ERalpha (alphaERKO) respectively. We show here that in both genders, ArKO(-/-) mice are vulnerable to beta-cell apoptosis and prone to insulin-deficient diabetes after exposure to acute oxidative stress with streptozotocin. In these mice, estradiol treatment rescues streptozotocin-induced beta-cell apoptosis, helps sustain insulin production, and prevents diabetes. In vitro, in mouse pancreatic islets and beta-cells exposed to oxidative stress, estradiol prevents apoptosis and protects insulin secretion. Estradiol protection is partially lost in beta-cells and islets treated with an ERalpha antagonist and in alphaERKO islets. Accordingly, alphaERKO mice are no longer protected by estradiol and display a gender nonspecific susceptibility to oxidative injury, precipitating beta-cell apoptosis and insulin-deficient diabetes. Finally, the predisposition to insulin deficiency can be mimicked in WT mice by pharmacological inhibition of ERalpha by using the antagonist tamoxifen. This study demonstrates that estradiol, acting, at least in part, through ERalpha, protects beta-cells from oxidative injury and prevents diabetes in mice of both genders.

authors

Le May C,Chu K,Hu M,Ortega CS,Simpson ER,Korach KS,Tsai MJ,Mauvais-Jarvis F

doi

10.1073/pnas.0602956103

subject

Has Abstract

pub_date

2006-06-13 00:00:00

pages

9232-7

issue

24

eissn

0027-8424

issn

1091-6490

pii

0602956103

journal_volume

103

pub_type

杂志文章
  • Antiestrogen-resistant subclones of MCF-7 human breast cancer cells are derived from a common monoclonal drug-resistant progenitor.

    abstract::Emergence of antiestrogen-resistant cells in MCF-7 cells during suppression of estrogen signaling is a widely accepted model of acquired breast cancer resistance to endocrine therapy. To obtain insight into the genomic basis of endocrine therapy resistance, we characterized MCF-7 monoclonal sublines that survived 21-d...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0907560106

    authors: Coser KR,Wittner BS,Rosenthal NF,Collins SC,Melas A,Smith SL,Mahoney CJ,Shioda K,Isselbacher KJ,Ramaswamy S,Shioda T

    更新日期:2009-08-25 00:00:00

  • Spectrum of cisplatin-induced mutations in Escherichia coli.

    abstract::Using a forward-mutation assay based on the inactivation of the tetracycline-resistance gene located on plasmid pBR322, we have determined the mutation spectrum induced in Escherichia coli by cisplatin [cis-diamminedichloroplatinum(II)], a widely used antitumor drug. Cisplatin is known to form mainly intrastrand diadd...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.84.11.3758

    authors: Burnouf D,Duane M,Fuchs RP

    更新日期:1987-06-01 00:00:00

  • Massive targeting of liposomes, surface-modified with anionized albumins, to hepatic endothelial cells.

    abstract::Human serum albumin (HSA) derivatized with cis-aconitic anhydride was covalently coupled to liposomes with a size of approximately 100 nm [polyaconitylated HSA (Aco-HSA) liposomes]. Within 30 min after injection into a rat, Aco-HSA liposomes were completely cleared from the blood and almost exclusively taken up by the...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.94.21.11681

    authors: Kamps JA,Morselt HW,Swart PJ,Meijer DK,Scherphof GL

    更新日期:1997-10-14 00:00:00

  • Viral serine palmitoyltransferase induces metabolic switch in sphingolipid biosynthesis and is required for infection of a marine alga.

    abstract::Marine viruses are the most abundant biological entities in the oceans shaping community structure and nutrient cycling. The interaction between the bloom-forming alga Emiliania huxleyi and its specific large dsDNA virus (EhV) is a major factor determining the fate of carbon in the ocean, thus serving as a key host-pa...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1523168113

    authors: Ziv C,Malitsky S,Othman A,Ben-Dor S,Wei Y,Zheng S,Aharoni A,Hornemann T,Vardi A

    更新日期:2016-03-29 00:00:00

  • Superantigenic character of an insert unique to SARS-CoV-2 spike supported by skewed TCR repertoire in patients with hyperinflammation.

    abstract::Multisystem Inflammatory Syndrome in Children (MIS-C) associated with COVID-19 is a newly recognized condition in children with recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. These children and adult patients with severe hyperinflammation present with a constellation of symptoms that st...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.2010722117

    authors: Cheng MH,Zhang S,Porritt RA,Noval Rivas M,Paschold L,Willscher E,Binder M,Arditi M,Bahar I

    更新日期:2020-10-13 00:00:00

  • The phosphatase and tensin homolog regulates epidermal growth factor receptor (EGFR) inhibitor response by targeting EGFR for degradation.

    abstract::The phosphatase and tensin homolog (PTEN) is a tumor suppressor that is inactivated in many human cancers. PTEN loss has been associated with resistance to inhibitors of the epidermal growth factor receptor (EGFR), but the molecular basis of this resistance is unclear. It is believed that unopposed phosphatidylinosito...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0911188107

    authors: Vivanco I,Rohle D,Versele M,Iwanami A,Kuga D,Oldrini B,Tanaka K,Dang J,Kubek S,Palaskas N,Hsueh T,Evans M,Mulholland D,Wolle D,Rajasekaran S,Rajasekaran A,Liau LM,Cloughesy TF,Dikic I,Brennan C,Wu H,Mischel PS,

    更新日期:2010-04-06 00:00:00

  • Alteration of epidermal growth factor-dependent phosphorylation during rat liver regeneration.

    abstract::Epidermal growth factor (EGF) stimulates membrane protein phosphorylation in a human cell line, A-431. The known hepatic mitogenic action of EGF and the reduction in EGF receptor number that occurs during liver regeneration led us to study whether EGF-dependent protein kinase activity was present in rat liver and whet...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.79.3.776

    authors: Rubin RA,O'Keefe EJ,Earp HS

    更新日期:1982-02-01 00:00:00

  • Complex pattern of Mycobacterium marinum gene expression during long-term granulomatous infection.

    abstract::During latent infection of humans with Mycobacterium tuberculosis, bacteria persist in the asymptomatic host within granulomas, organized collections of differentiated macrophages, and other immune cells. The mechanisms for persistence remain poorly understood, as is the metabolic and replicative state of the microbes...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.002024599

    authors: Chan K,Knaak T,Satkamp L,Humbert O,Falkow S,Ramakrishnan L

    更新日期:2002-03-19 00:00:00

  • Monosynaptic connections made by the sensory neurons of the gill- and siphon-withdrawal reflex in Aplysia participate in the storage of long-term memory for sensitization.

    abstract::We have found that in the gill- and siphon- withdrawal reflex of Aplysia, the memory for short-term sensitization grades smoothly into long-term memory with increased amounts of sensitization training. One cellular locus for the storage of the memory underlying short-term sensitization is the set of monosynaptic conne...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.82.23.8266

    authors: Frost WN,Castellucci VF,Hawkins RD,Kandel ER

    更新日期:1985-12-01 00:00:00

  • Rhythms of Drosophila period gene expression in culture.

    abstract::The Drosophila clock genes period (per) and timeless (tim) have been studied behaviorally and biochemically, but to date there has been no viable culture system for studying the cell biology of the Drosophila clock. We have cultured pupal ring glands attached to the central nervous system and observed rhythms of perio...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.94.8.4092

    authors: Emery IF,Noveral JM,Jamison CF,Siwicki KK

    更新日期:1997-04-15 00:00:00

  • Anacardic acid induces IL-33 and promotes remyelination in CNS.

    abstract::Given the known neuroreparative actions of IL-33 in experimental models of central nervous system (CNS) injury, we predicted that compounds which induce IL-33 are likely to promote remyelination. We found anacardic acid as a candidate molecule to serve as a therapeutic agent to promote remyelination. Addition of anaca...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.2006566117

    authors: Ljunggren-Rose Å,Natarajan C,Matta P,Pandey A,Upender I,Sriram S

    更新日期:2020-09-01 00:00:00

  • Femtosecond dynamics of rubredoxin: tryptophan solvation and resonance energy transfer in the protein.

    abstract::We report here studies of tryptophan (Trp) solvation dynamics in water and in the Pyrococcus furiosus rubredoxin protein, including the native and its apo and denatured forms. We also report results on energy transfer from Trp to the iron-sulfur [Fe-S] cluster. Trp fluorescence decay with the onset of solvation dynami...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.012582399

    authors: Zhong D,Pal SK,Zhang D,Chan SI,Zewail AH

    更新日期:2002-01-08 00:00:00

  • Apparent dependence of interactions between cytochrome b5 and cytochrome b5 reductase upon translational diffusion in dimyristoyl lecithin liposomes.

    abstract::Dimyristoyl lecithin liposomes, containing cytochrome b5 reductase (NADH:ferricytochrome b5 oxidoreductase, EC 1.6.2.2) and varying amounts of cytochrome b5, were used to measure flavoprotein catalysis alone and catalysis requiring electron transfer between the reductase and cytochrome as a function of temperature. Wh...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.72.7.2658

    authors: Strittmatter P,Rogers MJ

    更新日期:1975-07-01 00:00:00

  • "Ultraviolet footprinting" accurately maps sequence-specific contacts and DNA kinking in the EcoRI endonuclease-DNA complex.

    abstract::The "UV footprinting" technique has been used to detect contacts between EcoRI endonuclease and its recognition sequence at single nucleotide resolution. Comparison of the UV-footprinting results to the published crystal structure of the EcoRI endonuclease-DNA complex allows us to determine how UV light detects protei...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.85.17.6247

    authors: Becker MM,Lesser D,Kurpiewski M,Baranger A,Jen-Jacobson L

    更新日期:1988-09-01 00:00:00

  • A regulatory protein that interferes with activator-stimulated transcription in bacteria.

    abstract::Transcriptional activator proteins in bacteria often operate by interaction with the C-terminal domain of the alpha-subunit of RNA polymerase (RNAP). Here we report the discovery of an "anti-alpha" factor Spx in Bacillus subtilis that blocks transcriptional activation by binding to the alpha-C-terminal domain, thereby...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0637648100

    authors: Nakano S,Nakano MM,Zhang Y,Leelakriangsak M,Zuber P

    更新日期:2003-04-01 00:00:00

  • Cross-cultural recognition of basic emotions through nonverbal emotional vocalizations.

    abstract::Emotional signals are crucial for sharing important information, with conspecifics, for example, to warn humans of danger. Humans use a range of different cues to communicate to others how they feel, including facial, vocal, and gestural signals. We examined the recognition of nonverbal emotional vocalizations, such a...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0908239106

    authors: Sauter DA,Eisner F,Ekman P,Scott SK

    更新日期:2010-02-09 00:00:00

  • Allee effect in the selection for prime-numbered cycles in periodical cicadas.

    abstract::Periodical cicadas are well known for their prime-numbered life cycles (17 and 13 years) and their mass periodical emergences. The origination and persistence of prime-numbered cycles are explained by the hybridization hypothesis on the basis of their lower likelihood of hybridization with other cycles. Recently, we s...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0900215106

    authors: Tanaka Y,Yoshimura J,Simon C,Cooley JR,Tainaka K

    更新日期:2009-06-02 00:00:00

  • Ligand induction of a transcriptionally active thyroid hormone receptor coactivator complex.

    abstract::Transcriptional regulation by nuclear hormone receptors is thought to involve interactions with putative cofactors that may potentiate receptor function. Here we show that human thyroid hormone receptor alpha purified from HeLa cells grown in the presence of thyroid hormone (T3) is associated with a group of distinct ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.93.16.8329

    authors: Fondell JD,Ge H,Roeder RG

    更新日期:1996-08-06 00:00:00

  • Unexpected NO-dependent DNA binding by the CooA homolog from Carboxydothermus hydrogenoformans.

    abstract::CooA, the CO-sensing heme protein from Rhodospirillum rubrum, regulates the expression of genes that encode a CO-oxidation system, allowing R. rubrum to use CO as a sole energy source. To better understand the gas-sensing regulation mechanism used by R. rubrum CooA and its homologs in other organisms, we characterized...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0505919103

    authors: Clark RW,Lanz ND,Lee AJ,Kerby RL,Roberts GP,Burstyn JN

    更新日期:2006-01-24 00:00:00

  • Evidence of tectorial membrane radial motion in a propagating mode of a complex cochlear model.

    abstract::Knowledge of vibratory patterns in the cochlea is crucial to understanding the stimulation of mechanosensory cells. Experiments to determine the motion of the cochlear partition and surrounding fluid are extremely challenging. As a result, the motion data are incomplete and often contradictory. The bending mechanism o...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0401395101

    authors: Cai H,Shoelson B,Chadwick RS

    更新日期:2004-04-20 00:00:00

  • Elliptic Yang-Mills equation.

    abstract::We discuss some recent progress on the regularity theory of the elliptic Yang-Mills equation. We start with some basic properties of the elliptic Yang-Mills equation, such as Coulomb gauges, monotonicity, and curvature estimates. Next we discuss singularity of stationary Yang-Mills connections and compactness theorems...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.222494899

    authors: Tian G

    更新日期:2002-11-26 00:00:00

  • An algorithmic approach for breakage-fusion-bridge detection in tumor genomes.

    abstract::Breakage-fusion-bridge (BFB) is a mechanism of genomic instability characterized by the joining and subsequent tearing apart of sister chromatids. When this process is repeated during multiple rounds of cell division, it leads to patterns of copy number increases of chromosomal segments as well as fold-back inversions...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1220977110

    authors: Zakov S,Kinsella M,Bafna V

    更新日期:2013-04-02 00:00:00

  • Interleukin 7 (IL-7) selectively promotes mouse and human IL-17-producing γδ cells.

    abstract::IL-17-producing CD27(-) γδ cells (γδ(27-) cells) are widely viewed as innate immune cells that make critical contributions to host protection and autoimmunity. However, factors that promote them over IFN-γ-producing γδ(27+) cells are poorly elucidated. Moreover, although human IL-17-producing γδ cells are commonly imp...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1204327109

    authors: Michel ML,Pang DJ,Haque SF,Potocnik AJ,Pennington DJ,Hayday AC

    更新日期:2012-10-23 00:00:00

  • Structural basis for piRNA 2'-O-methylated 3'-end recognition by Piwi PAZ (Piwi/Argonaute/Zwille) domains.

    abstract::Argonaute and Piwi proteins are key players in the RNA silencing pathway, with the former interacting with micro-RNAs (miRNAs) and siRNAs, whereas the latter targets piwi-interacting RNAs (piRNAs) that are 2'-O-methylated (2(')-OCH(3)) at their 3' ends. Germline-specific piRNAs and Piwi proteins play a critical role i...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1017762108

    authors: Tian Y,Simanshu DK,Ma JB,Patel DJ

    更新日期:2011-01-18 00:00:00

  • Phosphorylation enzymes of the propionic acid bacteria and the roles of ATP inorganic pyrophosphate, and polyphosphates.

    abstract::It is shown that polyphosphates are not generated in significant amounts in the phosphoglycerate kinase reaction; polyphosphate is more effective than ATP in the formation of glucose 6-P by glucokinase, but the rate with ATP may be adequate to meet the requirements of glucose metabolism; PPi is far more effective than...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.82.2.312

    authors: Wood HG,Goss NH

    更新日期:1985-01-01 00:00:00

  • Molecular cloning of TRPC3a, an N-terminally extended, store-operated variant of the human C3 transient receptor potential channel.

    abstract::AK032317 is the GenBank accession no. of a full-length RIKEN mouse cDNA. It encodes a putative variant of the C3-type TRPC (transient receptor potential channel) that differs from the previously cloned murine TRPC3 cDNA in that it has a 5' extension stemming from inclusion of an additional exon (exon 0). The extended ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0409908102

    authors: Yildirim E,Kawasaki BT,Birnbaumer L

    更新日期:2005-03-01 00:00:00

  • The different tissue transcription patterns of genes for HNF-1, C/EBP, HNF-3, and HNF-4, protein factors that govern liver-specific transcription.

    abstract::The transcription factors that act in hepatocyte-specific gene expression include proteins that are present mainly in liver cells (HNF-1/LFB1, C/EBP, HNF-3, HNF-4) (HNF, hepatocyte nuclear factor; C/EBP, rat enhancer binding protein) and proteins that are widely distributed (AP-1, NF-1, NF-Y/ACF). We show here that th...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.88.9.3807

    authors: Xanthopoulos KG,Prezioso VR,Chen WS,Sladek FM,Cortese R,Darnell JE Jr

    更新日期:1991-05-01 00:00:00

  • Suppression of tumorigenicity by the wild-type tuberous sclerosis 2 (Tsc2) gene and its C-terminal region.

    abstract::The Tsc2 gene, which is mutationally inactivated in the germ line of some families with tuberous sclerosis, encodes a large, membrane-associated GTPase activating protein (GAP) designated tuberin. Studies of the Eker rat model of hereditary cancer strongly support the role of Tsc2 as a tumor suppressor gene. In this s...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.93.17.9154

    authors: Jin F,Wienecke R,Xiao GH,Maize JC Jr,DeClue JE,Yeung RS

    更新日期:1996-08-20 00:00:00

  • Truncated staphylococcal nuclease is compact but disordered.

    abstract::Deletion of 13 amino acids from the carboxyl terminus of the 149-amino acid staphylococcal nuclease molecule results in a denatured, partly unfolded molecule that lacks persistent secondary structure but is compact under physiological conditions. Since the modification is a carboxyl-terminal deletion, it is argued tha...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.89.2.748

    authors: Flanagan JM,Kataoka M,Shortle D,Engelman DM

    更新日期:1992-01-15 00:00:00

  • Stigmergy, collective actions, and animal social spacing.

    abstract::Collective animal behavior studies have led the way in developing models that account for a large number of individuals, but mostly have considered situations in which alignment and attraction play a key role, such as in schooling and flocking. By quantifying how animals react to one another's presence, when interacti...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1307071110

    authors: Giuggioli L,Potts JR,Rubenstein DI,Levin SA

    更新日期:2013-10-15 00:00:00