Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Subscribe

Logo for

Science 313 (5790): 1137-1140

Copyright © 2006 by the American Association for the Advancement of Science

Chemical Chaperones Reduce ER Stress and Restore Glucose Homeostasis in a Mouse Model of Type 2 Diabetes

Umut Özcan, Erkan Yilmaz, Lale Özcan, Masato Furuhashi, Eric Vaillancourt, Ross O. Smith, Cem Z. Görgün, Gökhan S. Hotamisligil*

Abstract: Endoplasmic reticulum (ER) stress is a key link between obesity, insulin resistance, and type 2 diabetes. Here, we provide evidence that this mechanistic link can be exploited for therapeutic purposes with orally active chemical chaperones. 4-Phenyl butyric acid and taurine-conjugated ursodeoxycholic acid alleviated ER stress in cells and whole animals. Treatment of obese and diabetic mice with these compounds resulted in normalization of hyperglycemia, restoration of systemic insulin sensitivity, resolution of fatty liver disease, and enhancement of insulin action in liver, muscle, and adipose tissues. Our results demonstrate that chemical chaperones enhance the adaptive capacity of the ER and act as potent antidiabetic modalities with potential application in the treatment of type 2 diabetes.

Department of Genetics and Complex Diseases, Harvard School of Public Health, Harvard University, Boston, MA 02115, USA.

* To whom correspondence should be addressed. E-mail: ghotamis{at}hsph.harvard.edu


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
A top-down systems biology view of microbiome-mammalian metabolic interactions in a mouse model.
F.-P. J. Martin, M.-E. Dumas, Y. Wang, C. Legido-Quigley, I. K. S. Yap, H. Tang, S. Zirah, G. M. Murphy, O. Cloarec, J. C. Lindon, et al. (2014)
Mol Syst Biol 3, 112
   Abstract »    Full Text »    PDF »
No Amelioration of Uromodulin Maturation and Trafficking Defect by Sodium 4-Phenylbutyrate in Vivo: STUDIES IN MOUSE MODELS OF UROMODULIN-ASSOCIATED KIDNEY DISEASE.
E. Kemter, S. Sklenak, B. Rathkolb, M. Hrabě de Angelis, E. Wolf, B. Aigner, and R. Wanke (2014)
J. Biol. Chem. 289, 10715-10726
   Abstract »    Full Text »    PDF »
Hyperglycaemic conditions perturb mouse oocyte in vitro developmental competence via beta-O-linked glycosylation of Heat shock protein 90.
L. A. Frank, M. L. Sutton-McDowall, H. M. Brown, D. L. Russell, R. B. Gilchrist, and J. G. Thompson (2014)
Hum. Reprod.
   Abstract »    Full Text »    PDF »
Attenuation of endoplasmic reticulum stress in Pelizaeus-Merzbacher disease by an anti-malaria drug, chloroquine.
T. Morimura, Y. Numata, S. Nakamura, E. Hirano, L. Gotoh, Y.-i. Goto, M. Urushitani, and K. Inoue (2014)
Experimental Biology and Medicine 239, 489-501
   Abstract »    Full Text »    PDF »
Inositol-requiring Enzyme 1 Inhibits Respiratory Syncytial Virus Replication.
I. Hassan, K. S. Gaines, W. J. Hottel, R. M. Wishy, S. E. Miller, L. S. Powers, D. T. Rutkowski, and M. M. Monick (2014)
J. Biol. Chem. 289, 7537-7546
   Abstract »    Full Text »    PDF »
Docosahexaenoic Acid Reduces ER Stress and Abnormal Protein Accumulation and Improves Neuronal Function Following Traumatic Brain Injury.
G. Begum, H. Q. Yan, L. Li, A. Singh, C. E. Dixon, and D. Sun (2014)
J. Neurosci. 34, 3743-3755
   Abstract »    Full Text »    PDF »
Wolfram Syndrome iPS Cells: The First Human Cell Model of Endoplasmic Reticulum Disease.
F. Urano (2014)
Diabetes 63, 844-846
   Full Text »    PDF »
Activation of mTORC1 in Collecting Ducts Causes Hyperkalemia.
Z. Chen, H. Dong, C. Jia, Q. Song, J. Chen, Y. Zhang, P. Lai, X. Fan, X. Zhou, M. Liu, et al. (2014)
J. Am. Soc. Nephrol. 25, 534-545
   Abstract »    Full Text »    PDF »
Reduction of endoplasmic reticulum stress attenuates the defects caused by Drosophila mitofusin depletion.
V. Debattisti, D. Pendin, E. Ziviani, A. Daga, and L. Scorrano (2014)
J. Cell Biol. 204, 303-312
   Abstract »    Full Text »    PDF »
Unfolded Protein Response Signaling and Metabolic Diseases.
J. Lee and U. Ozcan (2014)
J. Biol. Chem. 289, 1203-1211
   Abstract »    Full Text »    PDF »
Chemical chaperone treatment reduces intracellular accumulation of mutant collagen IV and ameliorates the cellular phenotype of a COL4A2 mutation that causes haemorrhagic stroke.
L. S. Murray, Y. Lu, A. Taggart, N. Van Regemorter, C. Vilain, M. Abramowicz, K. E. Kadler, and T. Van Agtmael (2014)
Hum. Mol. Genet. 23, 283-292
   Abstract »    Full Text »    PDF »
Ursodeoxycholic Acid Inhibits Liver X Receptor {alpha}-mediated Hepatic Lipogenesis via Induction of the Nuclear Corepressor SMILE.
J.-M. Lee, G.-T. Gang, D.-K. Kim, Y. D. Kim, S.-H. Koo, C.-H. Lee, and H.-S. Choi (2014)
J. Biol. Chem. 289, 1079-1091
   Abstract »    Full Text »    PDF »
Dysregulated phosphatidylinositol signaling promotes endoplasmic-reticulum-stress-mediated intestinal mucosal injury and inflammation in zebrafish.
P. C. Thakur, J. M. Davison, C. Stuckenholz, L. Lu, and N. Bahary (2014)
Dis. Model. Mech. 7, 93-106
   Abstract »    Full Text »    PDF »
Nuclear receptor LRH-1/NR5A2 is required and targetable for liver endoplasmic reticulum stress resolution.
J. L. Mamrosh, J. M. Lee, M. Wagner, P. J. Stambrook, R. J. Whitby, R. N. Sifers, S.-P. Wu, M.-J. Tsai, F. J. DeMayo, and D. D. Moore (2014)
eLife Sci 3, e01694
   Abstract »    Full Text »    PDF »
Acceleration of Biliary Cholesterol Secretion Restores Glycemic Control and Alleviates Hypertriglyceridemia in Obese db/db Mice.
K. Su, N. S. Sabeva, Y. Wang, X. Liu, J. D. Lester, J. Liu, S. Liang, and G. A. Graf (2014)
Arterioscler Thromb Vasc Biol 34, 26-33
   Abstract »    Full Text »    PDF »
Activating Transcription Factor 4 Links Metabolic Stress to Interleukin-6 Expression in Macrophages.
Y. Iwasaki, T. Suganami, R. Hachiya, I. Shirakawa, M. Kim-Saijo, M. Tanaka, M. Hamaguchi, T. Takai-Igarashi, M. Nakai, Y. Miyamoto, et al. (2014)
Diabetes 63, 152-161
   Abstract »    Full Text »    PDF »
CYP2J2-Derived Epoxyeicosatrienoic Acids Suppress Endoplasmic Reticulum Stress in Heart Failure.
X. Wang, L. Ni, L. Yang, Q. Duan, C. Chen, M. L. Edin, D. C. Zeldin, and D. W. Wang (2014)
Mol. Pharmacol. 85, 105-115
   Abstract »    Full Text »    PDF »
Effects of the green tea polyphenol epigallocatechin-3-gallate on high-fat diet-induced insulin resistance and endothelial dysfunction.
H.-J. Jang, S. D. Ridgeway, and J.-a. Kim (2013)
Am J Physiol Endocrinol Metab 305, E1444-E1451
   Abstract »    Full Text »    PDF »
Restoration of the Unfolded Protein Response in Pancreatic {beta} Cells Protects Mice Against Type 1 Diabetes.
F. Engin, A. Yermalovich, T. Nguyen, S. Hummasti, W. Fu, D. L. Eizirik, D. Mathis, and G. S. Hotamisligil (2013)
Science Translational Medicine 5, 211ra156
   Abstract »    Full Text »    PDF »
Endoplasmic reticulum stress is sufficient for the induction of IL-1{beta} production via activation of the NF-{kappa}B and inflammasome pathways.
S. Kim, Y. Joe, S. O. Jeong, M. Zheng, S. H. Back, S. W. Park, S. W. Ryter, and H. T. Chung (2013)
Innate Immunity
   Abstract »    Full Text »    PDF »
MCP-1-Induced Protein Promotes Endothelial-Like and Angiogenic Properties in Human Bone Marrow Monocytic Cells.
J. Niu, K. Wang, O. Zhelyabovska, Y. Saad, and P. E. Kolattukudy (2013)
J. Pharmacol. Exp. Ther. 347, 288-297
   Abstract »    Full Text »    PDF »
Endoplasmic Reticulum Stress Participates in Aortic Valve Calcification in Hypercholesterolemic Animals.
Z. Cai, F. Li, W. Gong, W. Liu, Q. Duan, C. Chen, L. Ni, Y. Xia, K. Cianflone, N. Dong, et al. (2013)
Arterioscler Thromb Vasc Biol 33, 2345-2354
   Abstract »    Full Text »    PDF »
Dexamethasone-induced selenoprotein S degradation is required for adipogenesis.
C. Y. Kim and K.-H. Kim (2013)
J. Lipid Res. 54, 2069-2082
   Abstract »    Full Text »    PDF »
Npas4 Is a Novel Activity-Regulated Cytoprotective Factor in Pancreatic {beta}-Cells.
P. V. Sabatini, N. A. J. Krentz, B. Zarrouki, C. Y. Westwell-Roper, C. Nian, R. A. Uy, A. M. J. Shapiro, V. Poitout, and F. C. Lynn (2013)
Diabetes 62, 2808-2820
   Abstract »    Full Text »    PDF »
Suppression of endoplasmic reticulum stress improves endothelium-dependent contractile responses in aorta of the spontaneously hypertensive rat.
K. M. Spitler, T. Matsumoto, and R. C. Webb (2013)
Am J Physiol Heart Circ Physiol 305, H344-H353
   Abstract »    Full Text »    PDF »
Sepsis: Multiple Abnormalities, Heterogeneous Responses, and Evolving Understanding.
K. N. Iskander, M. F. Osuchowski, D. J. Stearns-Kurosawa, S. Kurosawa, D. Stepien, C. Valentine, and D. G. Remick (2013)
Physiol Rev 93, 1247-1288
   Abstract »    Full Text »    PDF »
Low Molecular Weight Fucoidan Improves Endoplasmic Reticulum Stress-Reduced Insulin Sensitivity through AMP-Activated Protein Kinase Activation in L6 Myotubes and Restores Lipid Homeostasis in a Mouse Model of Type 2 Diabetes.
Y.-T. Jeong, Y. D. Kim, Y.-M. Jung, D.-C. Park, D.-S. Lee, S.-K. Ku, X. Li, Y. Lu, G. H. Chao, K.-J. Kim, et al. (2013)
Mol. Pharmacol. 84, 147-157
   Abstract »    Full Text »    PDF »
Obesity Induces Hypothalamic Endoplasmic Reticulum Stress and Impairs Proopiomelanocortin (POMC) Post-translational Processing.
I. Cakir, N. E. Cyr, M. Perello, B. P. Litvinov, A. Romero, R. C. Stuart, and E. A. Nillni (2013)
J. Biol. Chem. 288, 17675-17688
   Abstract »    Full Text »    PDF »
Activation of PPAR{alpha} Ameliorates Hepatic Insulin Resistance and Steatosis in High Fructose-Fed Mice Despite Increased Endoplasmic Reticulum Stress.
S. M. H. Chan, R.-Q. Sun, X.-Y. Zeng, Z.-H. Choong, H. Wang, M. J. Watt, and J.-M. Ye (2013)
Diabetes 62, 2095-2105
   Abstract »    Full Text »    PDF »
Soluble Epoxide Hydrolase Deficiency or Inhibition Attenuates Diet-induced Endoplasmic Reticulum Stress in Liver and Adipose Tissue.
A. Bettaieb, N. Nagata, D. AbouBechara, S. Chahed, C. Morisseau, B. D. Hammock, and F. G. Haj (2013)
J. Biol. Chem. 288, 14189-14199
   Abstract »    Full Text »    PDF »
Toll-like receptor 2 mediates high-fat diet-induced impairment of vasodilator actions of insulin.
H.-J. Jang, H.-S. Kim, D. H. Hwang, M. J. Quon, and J.-a. Kim (2013)
Am J Physiol Endocrinol Metab 304, E1077-E1088
   Abstract »    Full Text »    PDF »
Failure of the Adaptive Unfolded Protein Response in Islets of Obese Mice Is Linked With Abnormalities in {beta}-Cell Gene Expression and Progression to Diabetes.
J. Y. Chan, J. Luzuriaga, M. Bensellam, T. J. Biden, and D. R. Laybutt (2013)
Diabetes 62, 1557-1568
   Abstract »    Full Text »    PDF »
Insulin relaxes bladder via PI3K/AKT/eNOS pathway activation in mucosa: unfolded protein response-dependent insulin resistance as a cause of obesity-associated overactive bladder.
L. O. Leiria, C. Sollon, F. R. Bau, F. Z. Monica, C. L. D'Ancona, G. De Nucci, A. D. Grant, G. F. Anhe, and E. Antunes (2013)
J. Physiol. 591, 2259-2273
   Abstract »    Full Text »    PDF »
Hyperhomocysteinemia Promotes Insulin Resistance by Inducing Endoplasmic Reticulum Stress in Adipose Tissue.
Y. Li, H. Zhang, C. Jiang, M. Xu, Y. Pang, J. Feng, X. Xiang, W. Kong, G. Xu, Y. Li, et al. (2013)
J. Biol. Chem. 288, 9583-9592
   Abstract »    Full Text »    PDF »
Stimulation of Autophagy Improves Endoplasmic Reticulum Stress-Induced Diabetes.
E. Bachar-Wikstrom, J. D. Wikstrom, Y. Ariav, B. Tirosh, N. Kaiser, E. Cerasi, and G. Leibowitz (2013)
Diabetes 62, 1227-1237
   Abstract »    Full Text »    PDF »
Sodium Phenylbutyrate Enhances Astrocytic Neurotrophin Synthesis via Protein Kinase C (PKC)-mediated Activation of cAMP-response Element-binding Protein (CREB): IMPLICATIONS FOR ALZHEIMER DISEASE THERAPY.
G. T. Corbett, A. Roy, and K. Pahan (2013)
J. Biol. Chem. 288, 8299-8312
   Abstract »    Full Text »    PDF »
Membrane lipid saturation activates endoplasmic reticulum unfolded protein response transducers through their transmembrane domains.
R. Volmer, K. van der Ploeg, and D. Ron (2013)
PNAS 110, 4628-4633
   Abstract »    Full Text »    PDF »
Bile-acid-mediated decrease in endoplasmic reticulum stress: a potential contributor to the metabolic benefits of ileal interposition surgery in UCD-T2DM rats.
B. P. Cummings, A. Bettaieb, J. L. Graham, J. Kim, F. Ma, N. Shibata, K. L. Stanhope, C. Giulivi, F. Hansen, J. Jelsing, et al. (2013)
Dis. Model. Mech. 6, 443-456
   Abstract »    Full Text »    PDF »
Role of Endoplasmic Reticulum Stress in Diabetic Neuropathy.
N. E. Cameron (2013)
Diabetes 62, 696-697
   Full Text »    PDF »
Metabolic and Structural Effects of Phosphatidylcholine and Deoxycholate Injections on Subcutaneous Fat: A Randomized, Controlled Trial.
D. N. Reeds, B. S. Mohammed, S. Klein, C. B. Boswell, and V. L. Young (2013)
Aesthetic Surgery Journal 33, 400-408
   Abstract »    Full Text »    PDF »
Aberrant Endoplasmic Reticulum Stress in Vascular Smooth Muscle Increases Vascular Contractility and Blood Pressure in Mice Deficient of AMP-Activated Protein Kinase-{alpha}2 In Vivo.
B. Liang, S. Wang, Q. Wang, W. Zhang, B. Viollet, Y. Zhu, and M.-H. Zou (2013)
Arterioscler Thromb Vasc Biol 33, 595-604
   Abstract »    Full Text »    PDF »
Proteasome Dysfunction Mediates Obesity-Induced Endoplasmic Reticulum Stress and Insulin Resistance in the Liver.
T. Otoda, T. Takamura, H. Misu, T. Ota, S. Murata, H. Hayashi, H. Takayama, A. Kikuchi, T. Kanamori, K. R. Shima, et al. (2013)
Diabetes 62, 811-824
   Abstract »    Full Text »    PDF »
hCG-induced endoplasmic reticulum stress triggers apoptosis and reduces steroidogenic enzyme expression through activating transcription factor 6 in Leydig cells of the testis.
S.-J. Park, T.-S. Kim, C.-K. Park, S.-H. Lee, J.-M. Kim, K.-S. Lee, I.-k. Lee, J.-W. Park, M. A. Lawson, and D.-S. Lee (2013)
J. Mol. Endocrinol. 50, 151-166
   Abstract »    Full Text »    PDF »
ER stress potentiates insulin resistance through PERK-mediated FOXO phosphorylation.
W. Zhang, V. Hietakangas, S. Wee, S. C. Lim, J. Gunaratne, and S. M. Cohen (2013)
Genes & Dev. 27, 441-449
   Abstract »    Full Text »    PDF »
Xenobiotic Perturbation of ER Stress and the Unfolded Protein Response.
M. A. Lafleur, J. L. Stevens, and J. W. Lawrence (2013)
Toxicol Pathol 41, 235-262
   Abstract »    Full Text »    PDF »
c-Jun NH2-Terminal Kinase 1/2 and Endoplasmic Reticulum Stress as Interdependent and Reciprocal Causation in Diabetic Embryopathy.
X. Li, C. Xu, and P. Yang (2013)
Diabetes 62, 599-608
   Abstract »    Full Text »    PDF »
The Apoptosis Inhibitor ARC Alleviates the ER Stress Response to Promote {beta}-Cell Survival.
W. M. McKimpson, J. Weinberger, L. Czerski, M. Zheng, M. T. Crow, J. E. Pessin, S. C. Chua Jr., and R. N. Kitsis (2013)
Diabetes 62, 183-193
   Abstract »    Full Text »    PDF »
Attenuating Endoplasmic Reticulum Stress as a Novel Therapeutic Strategy in Pulmonary Hypertension.
P. Dromparis, R. Paulin, T. H. Stenson, A. Haromy, G. Sutendra, and E. D. Michelakis (2013)
Circulation 127, 115-125
   Abstract »    Full Text »    PDF »
Brown Rice and Its Component, {gamma}-Oryzanol, Attenuate the Preference for High-Fat Diet by Decreasing Hypothalamic Endoplasmic Reticulum Stress in Mice.
C. Kozuka, K. Yabiku, S. Sunagawa, R. Ueda, S.-i. Taira, H. Ohshiro, T. Ikema, K. Yamakawa, M. Higa, H. Tanaka, et al. (2012)
Diabetes 61, 3084-3093
   Abstract »    Full Text »    PDF »
Protein-Folding Homeostasis in the Endoplasmic Reticulum and Nutritional Regulation.
D. Ron and H. P. Harding (2012)
Cold Spring Harb Perspect Biol 4, a013177
   Abstract »    Full Text »    PDF »
Histone Deacetylase Inhibitor (HDACi) Suberoylanilide Hydroxamic Acid (SAHA)-mediated Correction of {alpha}1-Antitrypsin Deficiency.
M. Bouchecareilh, D. M. Hutt, P. Szajner, T. R. Flotte, and W. E. Balch (2012)
J. Biol. Chem. 287, 38265-38278
   Abstract »    Full Text »    PDF »
Vascular insulin resistance related to endoplasmic reticulum stress in aortas from a rat model of chronic kidney disease.
Q. G. Zhou, X. J. Fu, G. Y. Xu, W. Cao, H. F. Liu, J. Nie, M. Liang, and F. F. Hou (2012)
Am J Physiol Heart Circ Physiol 303, H1154-H1165
   Abstract »    Full Text »    PDF »
Counteracting chemical chaperone effects on the single-molecule {alpha}-synuclein structural landscape.
A. C. M. Ferreon, M. M. Moosa, Y. Gambin, and A. A. Deniz (2012)
PNAS 109, 17826-17831
   Abstract »    Full Text »    PDF »
Pharmacological Modulation of the Retinal Unfolded Protein Response in Bardet-Biedl Syndrome Reduces Apoptosis and Preserves Light Detection Ability.
A. Mockel, C. Obringer, T. B. M. Hakvoort, M. Seeliger, W. H. Lamers, C. Stoetzel, H. Dollfus, and V. Marion (2012)
J. Biol. Chem. 287, 37483-37494
   Abstract »    Full Text »    PDF »
p53 antagonizes the unfolded protein response and inhibits ground glass hepatocyte development during endoplasmic reticulum stress.
N. Dioufa, I. Chatzistamou, E. Farmaki, A. G. Papavassiliou, and H. Kiaris (2012)
Experimental Biology and Medicine 237, 1173-1180
   Abstract »    Full Text »    PDF »
Activation of the stress proteome as a mechanism for small molecule therapeutics.
R. D. Brose, G. Shin, M. C. McGuinness, T. Schneidereith, S. Purvis, G. X. Dong, J. Keefer, F. Spencer, and K. D. Smith (2012)
Hum. Mol. Genet. 21, 4237-4252
   Abstract »    Full Text »    PDF »
Aging Does Not Reduce Heat Shock Protein 70 in the Absence of Chronic Insulin Resistance.
K. Kavanagh, A. T. Wylie, T. J. Chavanne, M. J. Jorgensen, V. S. Voruganti, A. G. Comuzzie, J. R. Kaplan, C. E. McCall, and S. B. Kritchevsky (2012)
J Gerontol A Biol Sci Med Sci 67, 1014-1021
   Abstract »    Full Text »    PDF »
SEMA4A Mutations Lead to Susceptibility to Light Irradiation, Oxidative Stress, and ER Stress in Retinal Pigment Epithelial Cells.
K. Tsuruma, Y. Nishimura, S. Kishi, M. Shimazawa, T. Tanaka, and H. Hara (2012)
Invest. Ophthalmol. Vis. Sci. 53, 6729-6737
   Abstract »    Full Text »    PDF »
Induction of dsRNA-activated protein kinase links mitochondrial unfolded protein response to the pathogenesis of intestinal inflammation.
E. Rath, E. Berger, A. Messlik, T. Nunes, B. Liu, S. C. Kim, N. Hoogenraad, M. Sans, R. B. Sartor, and D. Haller (2012)
Gut 61, 1269-1278
   Abstract »    Full Text »    PDF »
Endoplasmic Reticulum Stress, Pancreatic {beta}-Cell Degeneration, and Diabetes.
F. R. Papa (2012)
Cold Spring Harb Perspect Med 2, a007666
   Abstract »    Full Text »    PDF »
In Vitro Amyloid Aggregate Forming Ability of TGFBI Mutants that Cause Corneal Dystrophies.
G. H.-F. Yam, K. Wang, V. Jhanji, K.-W. Choy, L. Baum, and C.-P. Pang (2012)
Invest. Ophthalmol. Vis. Sci. 53, 5890-5898
   Abstract »    Full Text »    PDF »
The ABCG5 ABCG8 Sterol Transporter Opposes the Development of Fatty Liver Disease and Loss of Glycemic Control Independently of Phytosterol Accumulation.
K. Su, N. S. Sabeva, J. Liu, Y. Wang, S. Bhatnagar, D. R. van der Westhuyzen, and G. A. Graf (2012)
J. Biol. Chem. 287, 28564-28575
   Abstract »    Full Text »    PDF »
Age- and diet-dependent requirement of DJ-1 for glucose homeostasis in mice with implications for human type 2 diabetes.
D. Jain, R. Jain, D. Eberhard, J. Eglinger, M. Bugliani, L. Piemonti, P. Marchetti, and E. Lammert (2012)
J Mol Cell Biol 4, 221-230
   Abstract »    Full Text »    PDF »
Phosphorylation of Adaptor Protein Containing Pleckstrin Homology Domain, Phosphotyrosine Binding Domain, and Leucine Zipper Motif 1 (APPL1) at Ser430 Mediates Endoplasmic Reticulum (ER) Stress-induced Insulin Resistance in Hepatocytes.
M. Liu, L. Zhou, L. Wei, R. Villarreal, X. Yang, D. Hu, R. A. Riojas, B. M. Holmes, P. R. Langlais, H. Lee, et al. (2012)
J. Biol. Chem. 287, 26087-26093
   Abstract »    Full Text »    PDF »
Reducing endoplasmic reticulum stress does not improve steatohepatitis in mice fed a methionine- and choline-deficient diet.
A. S. Henkel, A. M. Dewey, K. A. Anderson, S. Olivares, and R. M. Green (2012)
Am J Physiol Gastrointest Liver Physiol 303, G54-G59
   Abstract »    Full Text »    PDF »
Endoplasmic Reticulum Stress Is Involved in Cardiac Damage and Vascular Endothelial Dysfunction in Hypertensive Mice.
M. Kassan, M. Galan, M. Partyka, Z. Saifudeen, D. Henrion, M. Trebak, and K. Matrougui (2012)
Arterioscler Thromb Vasc Biol 32, 1652-1661
   Abstract »    Full Text »    PDF »
Stearic Acid Accumulation in Macrophages Induces Toll-Like Receptor 4/2-Independent Inflammation Leading to Endoplasmic Reticulum Stress-Mediated Apoptosis.
E. K. Anderson, A. A. Hill, and A. H. Hasty (2012)
Arterioscler Thromb Vasc Biol 32, 1687-1695
   Abstract »    Full Text »    PDF »
A Novel Role for Epidermal Growth Factor Receptor Tyrosine Kinase and Its Downstream Endoplasmic Reticulum Stress in Cardiac Damage and Microvascular Dysfunction in Type 1 Diabetes Mellitus.
M. Galan, M. Kassan, S.-K. Choi, M. Partyka, M. Trebak, D. Henrion, and K. Matrougui (2012)
Hypertension 60, 71-80
   Abstract »    Full Text »    PDF »
The impact of the unfolded protein response on human disease.
S. Wang and R. J. Kaufman (2012)
J. Cell Biol. 197, 857-867
   Abstract »    Full Text »    PDF »
Lecithin:Cholesterol Acyltransferase Deficiency Protects against Cholesterol-induced Hepatic Endoplasmic Reticulum Stress in Mice.
L. Hager, L. Li, H. Pun, L. Liu, M. A. Hossain, G. F. Maguire, M. Naples, C. Baker, L. Magomedova, J. Tam, et al. (2012)
J. Biol. Chem. 287, 20755-20768
   Abstract »    Full Text »    PDF »
Chemical Chaperone TUDCA Preserves Cone Photoreceptors in a Mouse Model of Leber Congenital Amaurosis.
T. Zhang, W. Baehr, and Y. Fu (2012)
Invest. Ophthalmol. Vis. Sci. 53, 3349-3356
   Abstract »    Full Text »    PDF »
Bile Acids Acutely Stimulate Insulin Secretion of Mouse {beta}-Cells via Farnesoid X Receptor Activation and KATP Channel Inhibition.
M. Dufer, K. Horth, R. Wagner, B. Schittenhelm, S. Prowald, T. F. J. Wagner, J. Oberwinkler, R. Lukowski, F. J. Gonzalez, P. Krippeit-Drews, et al. (2012)
Diabetes 61, 1479-1489
   Abstract »    Full Text »    PDF »
Chaperone Insufficiency Links TLR4 Protein Signaling to Endoplasmic Reticulum Stress.
A. Coope, M. Milanski, A. P. Arruda, L. M. Ignacio-Souza, M. J. Saad, G. F. Anhe, and L. A. Velloso (2012)
J. Biol. Chem. 287, 15580-15589
   Abstract »    Full Text »    PDF »
Suppression of adipose lipolysis by long-chain fatty acid analogs.
B. Kalderon, N. Azazmeh, N. Azulay, N. Vissler, M. Valitsky, and J. Bar-Tana (2012)
J. Lipid Res. 53, 868-878
   Abstract »    Full Text »    PDF »
Disturbance of Ca2+ Homeostasis Converts Pro-Met into Non-canonical Tyrosine Kinase p190MetNC in Response to Endoplasmic Reticulum Stress in MHCC97 Cells.
R. Dai, J. Li, J. Fu, Y. Chen, L. Yu, X. Zhao, Y. Qian, H. Zhang, H. Chen, Y. Ren, et al. (2012)
J. Biol. Chem. 287, 14586-14597
   Abstract »    Full Text »    PDF »
ER Stress as a Trigger for {beta}-Cell Dysfunction and Autoimmunity in Type 1 Diabetes.
B. O'Sullivan-Murphy and F. Urano (2012)
Diabetes 61, 780-781
   Full Text »    PDF »
Bariatric surgery to unload the stressed heart: a metabolic hypothesis.
M. F. Algahim, S. Sen, and H. Taegtmeyer (2012)
Am J Physiol Heart Circ Physiol 302, H1539-H1545
   Abstract »    Full Text »    PDF »
Lipid Peroxidation Product 4-Hydroxy-trans-2-nonenal Causes Endothelial Activation by Inducing Endoplasmic Reticulum Stress.
E. Vladykovskaya, S. D. Sithu, P. Haberzettl, N. S. Wickramasinghe, M. L. Merchant, B. G. Hill, J. McCracken, A. Agarwal, S. Dougherty, S. A. Gordon, et al. (2012)
J. Biol. Chem. 287, 11398-11409
   Abstract »    Full Text »    PDF »
Topical Ocular Sodium 4-Phenylbutyrate Rescues Glaucoma in a Myocilin Mouse Model of Primary Open-Angle Glaucoma.
G. S. Zode, K. E. Bugge, K. Mohan, S. D. Grozdanic, J. C. Peters, D. R. Koehn, M. G. Anderson, R. H. Kardon, E. M. Stone, and V. C. Sheffield (2012)
Invest. Ophthalmol. Vis. Sci. 53, 1557-1565
   Abstract »    Full Text »    PDF »
12/15-Lipoxygenase signaling in the endoplasmic reticulum stress response.
B. K. Cole, N. S. Kuhn, S. M. Green-Mitchell, K. A. Leone, R. M. Raab, J. L. Nadler, and S. K. Chakrabarti (2012)
Am J Physiol Endocrinol Metab 302, E654-E665
   Abstract »    Full Text »    PDF »
Functional RNA Interference (RNAi) Screen Identifies System A Neutral Amino Acid Transporter 2 (SNAT2) as a Mediator of Arsenic-induced Endoplasmic Reticulum Stress.
R. S. Oh, W.-C. Pan, A. Yalcin, H. Zhang, T. R. Guilarte, G. S. Hotamisligil, D. C. Christiani, and Q. Lu (2012)
J. Biol. Chem. 287, 6025-6034
   Abstract »    Full Text »    PDF »
Influenza A Viral Replication Is Blocked by Inhibition of the Inositol-requiring Enzyme 1 (IRE1) Stress Pathway.
I. H. Hassan, M. S. Zhang, L. S. Powers, J. Q. Shao, J. Baltrusaitis, D. T. Rutkowski, K. Legge, and M. M. Monick (2012)
J. Biol. Chem. 287, 4679-4689
   Abstract »    Full Text »    PDF »
Role of TRIB3 in Diabetic and Overnutrition-Induced Atherosclerosis.
J. R. Sowers (2012)
Diabetes 61, 265-266
   Full Text »    PDF »
Activation of Endoplasmic Reticulum Stress by Hyperglycemia Is Essential for Muller Cell-Derived Inflammatory Cytokine Production in Diabetes.
Y. Zhong, J. Li, Y. Chen, J. J. Wang, R. Ratan, and S. X. Zhang (2012)
Diabetes 61, 492-504
   Abstract »    Full Text »    PDF »
Dissociation of Inositol-requiring Enzyme (IRE1{alpha})-mediated c-Jun N-terminal Kinase Activation from Hepatic Insulin Resistance in Conditional X-box-binding Protein-1 (XBP1) Knock-out Mice.
M. J. Jurczak, A.-H. Lee, F. R. Jornayvaz, H.-Y. Lee, A. L. Birkenfeld, B. A. Guigni, M. Kahn, V. T. Samuel, L. H. Glimcher, and G. I. Shulman (2012)
J. Biol. Chem. 287, 2558-2567
   Abstract »    Full Text »    PDF »
TUDCA Slows Retinal Degeneration in Two Different Mouse Models of Retinitis Pigmentosa and Prevents Obesity in Bardet-Biedl Syndrome Type 1 Mice.
A. V. Drack, A. V. Dumitrescu, S. Bhattarai, D. Gratie, E. M. Stone, R. Mullins, and V. C. Sheffield (2012)
Invest. Ophthalmol. Vis. Sci. 53, 100-106
   Abstract »    Full Text »    PDF »
Endoplasmic Reticulum Stress Inhibits STAT3-Dependent Suppression of Hepatic Gluconeogenesis via Dephosphorylation and Deacetylation.
K. Kimura, T. Yamada, M. Matsumoto, Y. Kido, T. Hosooka, S.-i. Asahara, T. Matsuda, T. Ota, H. Watanabe, Y. Sai, et al. (2012)
Diabetes 61, 61-73
   Abstract »    Full Text »    PDF »
Histone deacetylase inhibitors prevent the degradation and restore the activity of glucocerebrosidase in Gaucher disease.
J. Lu, C. Yang, M. Chen, D. Y. Ye, R. R. Lonser, R. O. Brady, and Z. Zhuang (2011)
PNAS 108, 21200-21205
   Abstract »    Full Text »    PDF »
Mechanisms of ER Stress-Induced Apoptosis in Atherosclerosis.
C. M. Scull and I. Tabas (2011)
Arterioscler Thromb Vasc Biol 31, 2792-2797
   Abstract »    Full Text »    PDF »
Experimental evidence for therapeutic potential of taurine in the treatment of nonalcoholic fatty liver disease.
C. L. Gentile, A. M. Nivala, J. C. Gonzales, K. T. Pfaffenbach, D. Wang, Y. Wei, H. Jiang, D. J. Orlicky, D. R. Petersen, M. J. Pagliassotti, et al. (2011)
Am J Physiol Regulatory Integrative Comp Physiol 301, R1710-R1722
   Abstract »    Full Text »    PDF »
Chemical and Biological Approaches for Adapting Proteostasis to Ameliorate Protein Misfolding and Aggregation Diseases-Progress and Prognosis.
S. L. Lindquist and J. W. Kelly (2011)
Cold Spring Harb Perspect Biol 3, a004507
   Abstract »    Full Text »    PDF »

To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882