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Endoplasmic Reticulum Stress Links Obesity, Insulin Action, and Type 2 Diabetes
Umut Özcan,1*Qiong Cao,1*Erkan Yilmaz,1Ann-Hwee Lee,2Neal N. Iwakoshi,2Esra Özdelen,1Gürol Tuncman,1Cem Görgün,1Laurie H. Glimcher,2,3Gökhan S. Hotamisligil1
Obesity contributes to the development of type 2 diabetes, butthe underlying mechanisms are poorly understood. Using cellculture and mouse models, we show that obesity causes endoplasmicreticulum (ER) stress. This stress in turn leads to suppressionof insulin receptor signaling through hyperactivation of c-JunN-terminal kinase (JNK) and subsequent serine phosphorylationof insulin receptor substrate–1 (IRS-1). Mice deficientin X-box–binding protein–1 (XBP-1), a transcriptionfactor that modulates the ER stress response, develop insulinresistance. These findings demonstrate that ER stress is a centralfeature of peripheral insulin resistance and type 2 diabetesat the molecular, cellular, and organismal levels. Pharmacologicmanipulation of this pathway may offer novel opportunities fortreating these common diseases.
1 Department of Genetics and Complex Diseases, Harvard Medical School, Boston, MA 02115, USA. 2 Department of Immunology and Infectious Diseases, Harvard School of Public Health, Harvard Medical School, Boston, MA 02115, USA. 3 Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
* These authors contributed equally to this work.
To whom correspondence should be addressed. E-mail: ghotamis{at}hsph.harvard.edu
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M. Farias, C. Puebla, F. Westermeier, M. J. Jo, M. Pastor-Anglada, P. Casanello, and L. Sobrevia (2010)
Cardiovasc Res
86, 45-54
|Abstract »|Full Text »|PDF »
An Increase in the Circulating Concentration of Monocyte Chemoattractant Protein-1 Elicits Systemic Insulin Resistance Irrespective of Adipose Tissue Inflammation in Mice.
S. Tateya, Y. Tamori, T. Kawaguchi, H. Kanda, and M. Kasuga (2010)
Endocrinology
151, 971-979
|Abstract »|Full Text »|PDF »
Enhanced Signaling Downstream of Ribonucleic Acid-Activated Protein Kinase-Like Endoplasmic Reticulum Kinase Potentiates Lipotoxic Endoplasmic Reticulum Stress in Human Islets.
L. Ladriere, M. Igoillo-Esteve, D. A. Cunha, J.-P. Brion, M. Bugliani, P. Marchetti, D. L. Eizirik, and M. Cnop (2010)
J. Clin. Endocrinol. Metab.
95, 1442-1449
|Abstract »|Full Text »|PDF »
CD14+ Monocytes Are Vulnerable and Functionally Impaired Under Endoplasmic Reticulum Stress in Patients With Type 2 Diabetes.
T. Komura, Y. Sakai, M. Honda, T. Takamura, K. Matsushima, and S. Kaneko (2010)
Diabetes
59, 634-643
|Abstract »|Full Text »|PDF »
Hexosamine biosynthesis pathway flux promotes endoplasmic reticulum stress, lipid accumulation, and inflammatory gene expression in hepatic cells.
A. T Sage, L. A Walter, Y. Shi, M. I. Khan, H. Kaneto, A. Capretta, and G. H. Werstuck (2010)
Am J Physiol Endocrinol Metab
298, E499-E511
|Abstract »|Full Text »|PDF »
Exercise maintains euglycemia in association with decreased activation of c-Jun NH2-terminal kinase and serine phosphorylation of IRS-1 in the liver of ZDF rats.
M. A. Kiraly, J. Campbell, E. Park, H. E. Bates, J. T. Y. Yue, V. Rao, S. G. Matthews, G. Bikopoulos, M. Rozakis-Adcock, A. Giacca, et al. (2010)
Am J Physiol Endocrinol Metab
298, E671-E682
|Abstract »|Full Text »|PDF »
Mammalian Tribbles homolog 3 impairs insulin action in skeletal muscle: role in glucose-induced insulin resistance.
J. Liu, X. Wu, J. L. Franklin, J. L. Messina, H. S. Hill, D. R. Moellering, R. G. Walton, M. Martin, and W. T. Garvey (2010)
Am J Physiol Endocrinol Metab
298, E565-E576
|Abstract »|Full Text »|PDF »
Hepatic Bax Inhibitor-1 Inhibits IRE1{alpha} and Protects from Obesity-associated Insulin Resistance and Glucose Intolerance.
B. Bailly-Maitre, B. F. Belgardt, S. D. Jordan, B. Coornaert, M. John von Freyend, A. Kleinridders, J. Mauer, M. Cuddy, C. L. Kress, D. Willmes, et al. (2010)
J. Biol. Chem.
285, 6198-6207
|Abstract »|Full Text »|PDF »
Reduction of AMP-Activated Protein Kinase {alpha}2 Increases Endoplasmic Reticulum Stress and Atherosclerosis In Vivo.
Y. Dong, M. Zhang, B. Liang, Z. Xie, Z. Zhao, S. Asfa, H. C. Choi, and M.-H. Zou (2010)
Circulation
121, 792-803
|Abstract »|Full Text »|PDF »
Palmitate Attenuates Insulin Signaling and Induces Endoplasmic Reticulum Stress and Apoptosis in Hypothalamic Neurons: Rescue of Resistance and Apoptosis through Adenosine 5' Monophosphate-Activated Protein Kinase Activation.
Endoplasmic Reticulum Stress-Induced Activation of Activating Transcription Factor 6 Decreases cAMP-Stimulated Hepatic Gluconeogenesis via Inhibition of CREB.
H.-Y. Seo, M.-K. Kim, A.-K. Min, H.-S. Kim, S.-Y. Ryu, N.-K. Kim, K. M. Lee, H.-J. Kim, H.-S. Choi, K.-U. Lee, et al. (2010)
Endocrinology
151, 561-568
|Abstract »|Full Text »|PDF »
A Point Mutation in Sec61{alpha}1 Leads to Diabetes and Hepatosteatosis in Mice.
A Crucial Role for RACK1 in the Regulation of Glucose-Stimulated IRE1{alpha} Activation in Pancreatic {beta} Cells.
Y. Qiu, T. Mao, Y. Zhang, M. Shao, J. You, Q. Ding, Y. Chen, D. Wu, D. Xie, X. Lin, et al. (2010)
Science Signaling
3, ra7
|Abstract »|Full Text »|PDF »
Inflammation and adipose tissue macrophages in lipodystrophic mice.
L. Herrero, H. Shapiro, A. Nayer, J. Lee, and S. E. Shoelson (2010)
PNAS
107, 240-245
|Abstract »|Full Text »|PDF »
Grp78 Heterozygosity Promotes Adaptive Unfolded Protein Response and Attenuates Diet-Induced Obesity and Insulin Resistance.
R. Ye, D. Y. Jung, J. Y. Jun, J. Li, S. Luo, H. J. Ko, J. K. Kim, and A. S. Lee (2010)
Diabetes
59, 6-16
|Abstract »|Full Text »|PDF »
Deletion of Tumor Necrosis Factor-{alpha} Receptor 1 (TNFR1) Protects against Diet-induced Obesity by Means of Increased Thermogenesis.
T. Romanatto, E. A. Roman, A. P. Arruda, R. G. Denis, C. Solon, M. Milanski, J. C. Moraes, M. L. Bonfleur, G. R. Degasperi, P. K. Picardi, et al. (2009)
J. Biol. Chem.
284, 36213-36222
|Abstract »|Full Text »|PDF »
The chemical chaperone 4-phenylbutyrate inhibits adipogenesis by modulating the unfolded protein response.
S. Basseri, S. Lhotak, A. M. Sharma, and R. C. Austin (2009)
J. Lipid Res.
50, 2486-2501
|Abstract »|Full Text »|PDF »
Recent advances in understanding leptin signaling and leptin resistance.
D. L. Morris and L. Rui (2009)
Am J Physiol Endocrinol Metab
297, E1247-E1259
|Abstract »|Full Text »|PDF »
Homocysteine Supplementation Attenuates the Unfolded Protein Response in a Murine Nutritional Model of Steatohepatitis.
A. S. Henkel, M. S. Elias, and R. M. Green (2009)
J. Biol. Chem.
284, 31807-31816
|Abstract »|Full Text »|PDF »
Pdx1 (MODY4) regulates pancreatic beta cell susceptibility to ER stress.
M. M. Sachdeva, K. C. Claiborn, C. Khoo, J. Yang, D. N. Groff, R. G. Mirmira, and D. A. Stoffers (2009)
PNAS
106, 19090-19095
|Abstract »|Full Text »|PDF »
A Gluconeogenic Tryst in the Nucleus, with ER Stress as the Third Wheel.
Fenofibrate and PBA prevent fatty acid-induced loss of adiponectin receptor and pAMPK in human hepatoma cells and in hepatitis C virus-induced steatosis.
S. M. Rahman, I. Qadri, R. C. Janssen, and J. E. Friedman (2009)
J. Lipid Res.
50, 2193-2202
|Abstract »|Full Text »|PDF »
Identification of differentially expressed proteins in adipose tissue of divergently selected broilers.
Dissociation Between Fatty Liver and Insulin Resistance in Humans Carrying a Variant of the Patatin-Like Phospholipase 3 Gene.
K. Kantartzis, A. Peter, F. Machicao, J. Machann, S. Wagner, I. Konigsrainer, A. Konigsrainer, F. Schick, A. Fritsche, H.-U. Haring, et al. (2009)
Diabetes
58, 2616-2623
|Abstract »|Full Text »|PDF »
Inhibition of hepatic Niemann-Pick C1-like 1 improves hepatic insulin resistance.
M. Nomura, H. Ishii, A. Kawakami, and M. Yoshida (2009)
Am J Physiol Endocrinol Metab
297, E1030-E1038
|Abstract »|Full Text »|PDF »
Atf4 Regulates Obesity, Glucose Homeostasis, and Energy Expenditure.
J. Seo, E. S. Fortuno III, J. M. Suh, D. Stenesen, W. Tang, E. J. Parks, C. M. Adams, T. Townes, and J. M. Graff (2009)
Diabetes
58, 2565-2573
|Abstract »|Full Text »|PDF »
High-fat diets induce a rapid loss of the insulin anorectic response in the amygdala.
S. Boghossian, K. Lemmon, M. Park, and D. A. York (2009)
Am J Physiol Regulatory Integrative Comp Physiol
297, R1302-R1311
|Abstract »|Full Text »|PDF »
O-GlcNAc signaling attenuates ER stress-induced cardiomyocyte death.
G. A. Ngoh, T. Hamid, S. D. Prabhu, and S. P. Jones (2009)
Am J Physiol Heart Circ Physiol
297, H1711-H1719
|Abstract »|Full Text »|PDF »
Function of IRE1 alpha in the placenta is essential for placental development and embryonic viability.
T. Iwawaki, R. Akai, S. Yamanaka, and K. Kohno (2009)
PNAS
106, 16657-16662
|Abstract »|Full Text »|PDF »
Role of ERO1-{alpha}-mediated stimulation of inositol 1,4,5-triphosphate receptor activity in endoplasmic reticulum stress-induced apoptosis.
G. Li, M. Mongillo, K.-T. Chin, H. Harding, D. Ron, A. R. Marks, and I. Tabas (2009)
J. Cell Biol.
186, 783-792
|Abstract »|Full Text »|PDF »
The Constitutive Androstane Receptor Is an Anti-obesity Nuclear Receptor That Improves Insulin Sensitivity.
J. Gao, J. He, Y. Zhai, T. Wada, and W. Xie (2009)
J. Biol. Chem.
284, 25984-25992
|Abstract »|Full Text »|PDF »
L. Zhou, J. Zhang, Q. Fang, M. Liu, X. Liu, W. Jia, L. Q. Dong, and F. Liu (2009)
Mol. Pharmacol.
76, 596-603
|Abstract »|Full Text »|PDF »
Vascular actions of insulin with implications for endothelial dysfunction.
M. A. Potenza, F. Addabbo, and M. Montagnani (2009)
Am J Physiol Endocrinol Metab
297, E568-E577
|Abstract »|Full Text »|PDF »
Raptor Binds the SAIN (Shc and IRS-1 NPXY Binding) Domain of Insulin Receptor Substrate-1 (IRS-1) and Regulates the Phosphorylation of IRS-1 at Ser-636/639 by mTOR.
Individual Stearoyl-CoA Desaturase 1 Expression Modulates Endoplasmic Reticulum Stress and Inflammation in Human Myotubes and Is Associated With Skeletal Muscle Lipid Storage and Insulin Sensitivity In Vivo.
A. Peter, C. Weigert, H. Staiger, F. Machicao, F. Schick, J. Machann, N. Stefan, C. Thamer, H.-U. Haring, and E. Schleicher (2009)
Diabetes
58, 1757-1765
|Abstract »|Full Text »|PDF »
M. I. Lefterova, S. E. Mullican, T. Tomaru, M. Qatanani, M. Schupp, and M. A. Lazar (2009)
Diabetes
58, 1879-1886
|Abstract »|Full Text »|PDF »
Activated Ask1-MKK4-p38MAPK/JNK Stress Signaling Pathway in Human Omental Fat Tissue May Link Macrophage Infiltration to Whole-Body Insulin Sensitivity.
M. Bluher, N. Bashan, I. Shai, I. Harman-Boehm, T. Tarnovscki, E. Avinaoch, M. Stumvoll, A. Dietrich, N. Kloting, and A. Rudich (2009)
J. Clin. Endocrinol. Metab.
94, 2507-2515
|Abstract »|Full Text »|PDF »
The ortholog of human solute carrier family 35 member B1 (UDP-galactose transporter-related protein 1) is involved in maintenance of ER homeostasis and essential for larval development in Caenorhabditis elegans.
K. Dejima, D. Murata, S. Mizuguchi, K. H. Nomura, K. Gengyo-Ando, S. Mitani, S. Kamiyama, S. Nishihara, and K. Nomura (2009)
FASEB J
23, 2215-2225
|Abstract »|Full Text »|PDF »
The Orphan Nuclear Receptor ROR{alpha} Restrains Adipocyte Differentiation through a Reduction of C/EBP{beta} Activity and Perilipin Gene Expression.
N. Ohoka, S. Kato, Y. Takahashi, H. Hayashi, and R. Sato (2009)
Mol. Endocrinol.
23, 759-771
|Abstract »|Full Text »|PDF »
Getting the message across: mechanisms of physiological cross talk by adipose tissue.
D.-E. Lee, S. Kehlenbrink, H. Lee, M. Hawkins, and J. S. Yudkin (2009)
Am J Physiol Endocrinol Metab
296, E1210-E1229
|Abstract »|Full Text »|PDF »
Dysregulated glutathione metabolism links to impaired insulin action in adipocytes.
H. Kobayashi, M. Matsuda, A. Fukuhara, R. Komuro, and I. Shimomura (2009)
Am J Physiol Endocrinol Metab
296, E1326-E1334
|Abstract »|Full Text »|PDF »
Palmitate Induces Insulin Resistance in H4IIEC3 Hepatocytes through Reactive Oxygen Species Produced by Mitochondria.
S. Nakamura, T. Takamura, N. Matsuzawa-Nagata, H. Takayama, H. Misu, H. Noda, S. Nabemoto, S. Kurita, T. Ota, H. Ando, et al. (2009)
J. Biol. Chem.
284, 14809-14818
|Abstract »|Full Text »|PDF »
Sustained activation of XBP1 splicing leads to endothelial apoptosis and atherosclerosis development in response to disturbed flow.
L. Zeng, A. Zampetaki, A. Margariti, A. E. Pepe, S. Alam, D. Martin, Q. Xiao, W. Wang, Z.-G. Jin, G. Cockerill, et al. (2009)
PNAS
106, 8326-8331
|Abstract »|Full Text »|PDF »
Maternal nutrient restriction during pregnancy differentially alters the unfolded protein response in adipose and renal tissue of obese juvenile offspring.
D. Sharkey, D. S. Gardner, H. P. Fainberg, S. Sebert, P. Bos, V. Wilson, R. Bell, M. E. Symonds, and H. Budge (2009)
FASEB J
23, 1314-1324
|Abstract »|Full Text »|PDF »
Effects of palmitate on ER and cytosolic Ca2+ homeostasis in {beta}-cells.
K. S. Gwiazda, T.-L. B. Yang, Y. Lin, and J. D. Johnson (2009)
Am J Physiol Endocrinol Metab
296, E690-E701
|Abstract »|Full Text »|PDF »
Dual suppression of adipogenesis by cigarette smoke through activation of the aryl hydrocarbon receptor and induction of endoplasmic reticulum stress.
T. Shimada, N. Hiramatsu, K. Hayakawa, S. Takahashi, A. Kasai, Y. Tagawa, M. Mukai, J. Yao, Y. Fujii-Kuriyama, and M. Kitamura (2009)
Am J Physiol Endocrinol Metab
296, E721-E730
|Abstract »|Full Text »|PDF »
Asymmetrical dimethylarginine triggers lipolysis and inflammatory response via induction of endoplasmic reticulum stress in cultured adipocytes.
Q. G. Zhou, M. Zhou, F. F. Hou, and X. Peng (2009)
Am J Physiol Endocrinol Metab
296, E869-E878
|Abstract »|Full Text »|PDF »
Examination of 'lipotoxicity' in skeletal muscle of high-fat fed and ob/ob mice.
S. M. Turpin, J. G. Ryall, R. Southgate, I. Darby, A. L. Hevener, M. A. Febbraio, B. E. Kemp, G. S. Lynch, and M. J. Watt (2009)
J. Physiol.
587, 1593-1605
|Abstract »|Full Text »|PDF »
The Non-coding RNA gadd7 Is a Regulator of Lipid-induced Oxidative and Endoplasmic Reticulum Stress.
R. T. Brookheart, C. I. Michel, L. L. Listenberger, D. S. Ory, and J. E. Schaffer (2009)
J. Biol. Chem.
284, 7446-7454
|Abstract »|Full Text »|PDF »
Pathogenesis of retinitis pigmentosa associated with apoptosis-inducing mutations in carbonic anhydrase IV.
R. Datta, A. Waheed, G. Bonapace, G. N. Shah, and W. S. Sly (2009)
PNAS
106, 3437-3442
|Abstract »|Full Text »|PDF »
Endoplasmic Reticulum Stress Is Reduced in Tissues of Obese Subjects After Weight Loss.
M. F. Gregor, L. Yang, E. Fabbrini, B. S. Mohammed, J. C. Eagon, G. S. Hotamisligil, and S. Klein (2009)
Diabetes
58, 693-700
|Abstract »|Full Text »|PDF »
Liver-Specific Deletion of Protein-Tyrosine Phosphatase 1B (PTP1B) Improves Metabolic Syndrome and Attenuates Diet-Induced Endoplasmic Reticulum Stress.
M. Delibegovic, D. Zimmer, C. Kauffman, K. Rak, E.-G. Hong, Y.-R. Cho, J. K. Kim, B. B. Kahn, B. G. Neel, and K. K. Bence (2009)
Diabetes
58, 590-599
|Abstract »|Full Text »|PDF »
Relationship Between Functional Promoter Polymorphism in the XBP1 Gene (-116C/G) and Obesity.
E. Yilmaz, M. Berberoglu, and N. Akar (2009)
Clinical and Applied Thrombosis/Hemostasis
16, 99-102
|Abstract »|PDF »
Imatinib Mesylate Reduces Endoplasmic Reticulum Stress and Induces Remission of Diabetes in db/db Mice.
M. S. Han, K. W. Chung, H. G. Cheon, S. D. Rhee, C.-H. Yoon, M.-K. Lee, K.-W. Kim, and M.-S. Lee (2009)
Diabetes
58, 329-336
|Abstract »|Full Text »|PDF »
Roles of IP3R and RyR Ca2+ Channels in Endoplasmic Reticulum Stress and {beta}-Cell Death.
D. S. Luciani, K. S. Gwiazda, T.-L. B. Yang, T. B. Kalynyak, Y. Bychkivska, M. H.Z. Frey, K. D. Jeffrey, A. V. Sampaio, T. M. Underhill, and J. D. Johnson (2009)
Diabetes
58, 422-432
|Abstract »|Full Text »|PDF »
Saturated Fatty Acids Produce an Inflammatory Response Predominantly through the Activation of TLR4 Signaling in Hypothalamus: Implications for the Pathogenesis of Obesity.
M. Milanski, G. Degasperi, A. Coope, J. Morari, R. Denis, D. E. Cintra, D. M. L. Tsukumo, G. Anhe, M. E. Amaral, H. K. Takahashi, et al. (2009)
J. Neurosci.
29, 359-370
|Abstract »|Full Text »|PDF »
Positive and Negative Regulation of Insulin Signaling by Reactive Oxygen and Nitrogen Species.
N. Bashan, J. Kovsan, I. Kachko, H. Ovadia, and A. Rudich (2009)
Physiol Rev
89, 27-71
|Abstract »|Full Text »|PDF »
Palmitate- and lipopolysaccharide-activated macrophages evoke contrasting insulin responses in muscle cells.
V. Samokhvalov, P. J. Bilan, J. D. Schertzer, C. N. Antonescu, and A. Klip (2009)
Am J Physiol Endocrinol Metab
296, E37-E46
|Abstract »|Full Text »|PDF »
Valproate Attenuates Accelerated Atherosclerosis in Hyperglycemic ApoE-Deficient Mice: Evidence in Support of a Role for Endoplasmic Reticulum Stress and Glycogen Synthase Kinase-3 in Lesion Development and Hepatic Steatosis.
A. J. Bowes, M. I. Khan, Y. Shi, L. Robertson, and G. H. Werstuck (2009)
Am. J. Pathol.
174, 330-342
|Abstract »|Full Text »|PDF »
Extracellular Nampt Promotes Macrophage Survival via a Nonenzymatic Interleukin-6/STAT3 Signaling Mechanism.
Y. Li, Y. Zhang, B. Dorweiler, D. Cui, T. Wang, C. W. Woo, C. S. Brunkan, C. Wolberger, S.-i. Imai, and I. Tabas (2008)
J. Biol. Chem.
283, 34833-34843
|Abstract »|Full Text »|PDF »
Causes and Metabolic Consequences of Fatty Liver.
N. Stefan, K. Kantartzis, and H.-U. Haring (2008)
Endocr. Rev.
29, 939-960
|Abstract »|Full Text »|PDF »
The Metabolic Syndrome.
M.-A. Cornier, D. Dabelea, T. L. Hernandez, R. C. Lindstrom, A. J. Steig, N. R. Stob, R. E. Van Pelt, H. Wang, and R. H. Eckel (2008)
Endocr. Rev.
29, 777-822
|Abstract »|Full Text »|PDF »
T. Hosoi, M. Sasaki, T. Miyahara, C. Hashimoto, S. Matsuo, M. Yoshii, and K. Ozawa (2008)
Mol. Pharmacol.
74, 1610-1619
|Abstract »|Full Text »|PDF »
Endoplasmic Reticulum Stress Markers Are Associated with Obesity in Nondiabetic Subjects.
N. K. Sharma, S. K. Das, A. K. Mondal, O. G. Hackney, W. S. Chu, P. A. Kern, N. Rasouli, H. J. Spencer, A. Yao-Borengasser, and S. C. Elbein (2008)
J. Clin. Endocrinol. Metab.
93, 4532-4541
|Abstract »|Full Text »|PDF »
Vascular Inflammation, Insulin Resistance, and Reduced Nitric Oxide Production Precede the Onset of Peripheral Insulin Resistance.
F. Kim, M. Pham, E. Maloney, N. O. Rizzo, G. J. Morton, B. E. Wisse, E. A. Kirk, A. Chait, and M. W. Schwartz (2008)
Arterioscler Thromb Vasc Biol
28, 1982-1988
|Abstract »|Full Text »|PDF »
Cytokine-Induced {beta}-Cell Death Is Independent of Endoplasmic Reticulum Stress Signaling.
M. C. Akerfeldt, J. Howes, J. Y. Chan, V. A. Stevens, N. Boubenna, H. M. McGuire, C. King, T. J. Biden, and D. R. Laybutt (2008)
Diabetes
57, 3034-3044
|Abstract »|Full Text »|PDF »
The emerging biology of adipose tissue in chronic kidney disease: from fat to facts.
J. Axelsson (2008)
Nephrol. Dial. Transplant.
23, 3041-3046
|Full Text »|PDF »
Increase in Endoplasmic Reticulum Stress-Related Proteins and Genes in Adipose Tissue of Obese, Insulin-Resistant Individuals.
G. Boden, X. Duan, C. Homko, E. J. Molina, W. Song, O. Perez, P. Cheung, and S. Merali (2008)
Diabetes
57, 2438-2444
|Abstract »|Full Text »|PDF »
Reduction of JNK1 expression with antisense oligonucleotide improves adiposity in obese mice.
X. X. Yu, S. F. Murray, L. Watts, S. L. Booten, J. Tokorcheck, B. P. Monia, and S. Bhanot (2008)
Am J Physiol Endocrinol Metab
295, E436-E445
|Abstract »|Full Text »|PDF »
Effect of pioglitazone treatment on endoplasmic reticulum stress response in human adipose and in palmitate-induced stress in human liver and adipose cell lines.
S. K. Das, W. S. Chu, A. K. Mondal, N. K. Sharma, P. A. Kern, N. Rasouli, and S. C. Elbein (2008)
Am J Physiol Endocrinol Metab
295, E393-E400
|Abstract »|Full Text »|PDF »
Initiation and execution of lipotoxic ER stress in pancreatic {beta}-cells.
D. A. Cunha, P. Hekerman, L. Ladriere, A. Bazarra-Castro, F. Ortis, M. C. Wakeham, F. Moore, J. Rasschaert, A. K. Cardozo, E. Bellomo, et al. (2008)
J. Cell Sci.
121, 2308-2318
|Abstract »|Full Text »|PDF »
Carboxypeptidase E mediates palmitate-induced {beta}-cell ER stress and apoptosis.
K. D. Jeffrey, E. U. Alejandro, D. S. Luciani, T. B. Kalynyak, X. Hu, H. Li, Y. Lin, R. R. Townsend, K. S. Polonsky, and J. D. Johnson (2008)
PNAS
105, 8452-8457
|Abstract »|Full Text »|PDF »
Protein Kinase C{theta} Is Required for Autophagy in Response to Stress in the Endoplasmic Reticulum.
K. Sakaki, J. Wu, and R. J. Kaufman (2008)
J. Biol. Chem.
283, 15370-15380
|Abstract »|Full Text »|PDF »
The Unfolded Protein Response: A Pathway That Links Insulin Demand with {beta}-Cell Failure and Diabetes.
Liver gene expression analysis reveals endoplasmic reticulum stress and metabolic dysfunction in SCD1-deficient mice fed a very low-fat diet.
M. T. Flowers, M. P. Keller, Y. Choi, H. Lan, C. Kendziorski, J. M. Ntambi, and A. D. Attie (2008)
Physiol Genomics
33, 361-372
|Abstract »|Full Text »|PDF »
TRB3 suppresses adipocyte differentiation by negatively regulating PPAR{gamma} transcriptional activity.
Y. Takahashi, N. Ohoka, H. Hayashi, and R. Sato (2008)
J. Lipid Res.
49, 880-892
|Abstract »|Full Text »|PDF »
Inhibition of Foxo1 Protects Pancreatic Islet {beta}-Cells Against Fatty Acid and Endoplasmic Reticulum Stress-Induced Apoptosis.
S. C. Martinez, K. Tanabe, C. Cras-Meneur, N. A. Abumrad, E. Bernal-Mizrachi, and M. A. Permutt (2008)
Diabetes
57, 846-859
|Abstract »|Full Text »|PDF »
Quantitative Linkage Analysis for Pancreatic B-cell Function and Insulin Resistance in a Large Twin Cohort.
M. Falchi, S. G. Wilson, D. Paximadas, R. Swaminathan, and T. D. Spector (2008)
Diabetes
57, 1120-1124
|Abstract »|Full Text »|PDF »
Commonality of functional annotation: a method for prioritization of candidate genes from genome-wide linkage studies.
D. Shriner, T. M. Baye, M. A. Padilla, S. Zhang, L. K. Vaughan, and A. E. Loraine (2008)
Nucleic Acids Res.
36, e26
|Abstract »|Full Text »|PDF »
Therapeutic Potential of Peroxisome Proliferators-Activated Receptor-{alpha}/{gamma} Dual Agonist With Alleviation of Endoplasmic Reticulum Stress for the Treatment of Diabetes.
K. L. Han, J. S. Choi, J. Y. Lee, J. Song, M. K. Joe, M. H. Jung, and J.-K. Hwang (2008)
Diabetes
57, 737-745
|Abstract »|Full Text »|PDF »
Differential activation of ER stress and apoptosis in response to chronically elevated free fatty acids in pancreatic {beta}-cells.
E. Lai, G. Bikopoulos, M. B. Wheeler, M. Rozakis-Adcock, and A. Volchuk (2008)
Am J Physiol Endocrinol Metab
294, E540-E550
|Abstract »|Full Text »|PDF »
HSP72 protects against obesity-induced insulin resistance.
J. Chung, A.-K. Nguyen, D. C. Henstridge, A. G. Holmes, M. H. S. Chan, J. L. Mesa, G. I. Lancaster, R. J. Southgate, C. R. Bruce, S. J. Duffy, et al. (2008)
PNAS
105, 1739-1744
|Abstract »|Full Text »|PDF »
The Role for Endoplasmic Reticulum Stress in Diabetes Mellitus.
Sequential phosphorylation of insulin receptor substrate-2 by glycogen synthase kinase-3 and c-Jun NH2-terminal kinase plays a role in hepatic insulin signaling.
H. Sharfi and H. Eldar-Finkelman (2008)
Am J Physiol Endocrinol Metab
294, E307-E315
|Abstract »|Full Text »|PDF »
Local activation of the I{kappa}K-NF-{kappa}B pathway in muscle does not cause insulin resistance.
E. Polkinghorne, Q. Lau, G. J. Cooney, E. W. Kraegen, and M. E. Cleasby (2008)
Am J Physiol Endocrinol Metab
294, E316-E325
|Abstract »|Full Text »|PDF »
Diabetes and Obesity: Part 1.
Z. T. Bloomgarden (2007)
Diabetes Care
30, 3145-3151
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Obesity-Induced Inflammation in White Adipose Tissue Is Attenuated by Loss of Melanocortin-3 Receptor Signaling.
K. L. J. Ellacott, J. G. Murphy, D. L. Marks, and R. D. Cone (2007)
Endocrinology
148, 6186-6194
|Abstract »|Full Text »|PDF »
Essential Role of Mitochondrial Function in Adiponectin Synthesis in Adipocytes.
E. H. Koh, J.-Y. Park, H.-S. Park, M. J. Jeon, J. W. Ryu, M. Kim, S. Y. Kim, M.-S. Kim, S.-W. Kim, I. S. Park, et al. (2007)
Diabetes
56, 2973-2981
|Abstract »|Full Text »|PDF »
The Role of Brain-derived Neurotrophic Factor (BDNF)-induced XBP1 Splicing during Brain Development.
A. Hayashi, T. Kasahara, K. Iwamoto, M. Ishiwata, M. Kametani, C. Kakiuchi, T. Furuichi, and T. Kato (2007)
J. Biol. Chem.
282, 34525-34534
|Abstract »|Full Text »|PDF »
HIV-1 Protease Inhibitors Nelfinavir and Atazanavir Induce Malignant Glioma Death by Triggering Endoplasmic Reticulum Stress.
P. Pyrko, A. Kardosh, W. Wang, W. Xiong, A. H. Schonthal, and T. C. Chen (2007)
Cancer Res.
67, 10920-10928
|Abstract »|Full Text »|PDF »
Activation of Endoplasmic Reticulum Stress in Degenerating Photoreceptors of the rd1 Mouse.
L.-p. Yang, L.-m. Wu, X.-j. Guo, and M. O. M. Tso (2007)
Invest. Ophthalmol. Vis. Sci.
48, 5191-5198
|Abstract »|Full Text »|PDF »
Disruption of CXC Motif Chemokine Ligand-14 in Mice Ameliorates Obesity-induced Insulin Resistance.
N. Nara, Y. Nakayama, S. Okamoto, H. Tamura, M. Kiyono, M. Muraoka, K. Tanaka, C. Taya, H. Shitara, R. Ishii, et al. (2007)
J. Biol. Chem.
282, 30794-30803
|Abstract »|Full Text »|PDF »
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