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.

Logo for

Science 306 (5695): 457-461

Copyright © 2004 by the American Association for the Advancement of Science

Endoplasmic Reticulum Stress Links Obesity, Insulin Action, and Type 2 Diabetes

Umut Özcan,1* Qiong Cao,1* Erkan Yilmaz,1 Ann-Hwee Lee,2 Neal N. Iwakoshi,2 Esra Özdelen,1 Gürol Tuncman,1 Cem Görgün,1 Laurie H. Glimcher,2,3 Gökhan S. Hotamisligil1{dagger}

Abstract: Obesity contributes to the development of type 2 diabetes, but the underlying mechanisms are poorly understood. Using cell culture and mouse models, we show that obesity causes endoplasmic reticulum (ER) stress. This stress in turn leads to suppression of insulin receptor signaling through hyperactivation of c-Jun N-terminal kinase (JNK) and subsequent serine phosphorylation of insulin receptor substrate–1 (IRS-1). Mice deficient in X-box–binding protein–1 (XBP-1), a transcription factor that modulates the ER stress response, develop insulin resistance. These findings demonstrate that ER stress is a central feature of peripheral insulin resistance and type 2 diabetes at the molecular, cellular, and organismal levels. Pharmacologic manipulation of this pathway may offer novel opportunities for treating 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.

Back to Top

* These authors contributed equally to this work.

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

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Role of TRIB3 in Diabetic and Overnutrition-Induced Atherosclerosis.
J. R. Sowers (2012)
Diabetes 61, 265-266
   Full Text »    PDF »
Systemic SIRT1 insufficiency results in disruption of energy homeostasis and steroid hormone metabolism upon high-fat-diet feeding.
A. Purushotham, Q. Xu, and X. Li (2012)
FASEB J 26, 656-667
   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 »
O2 Regulates Skeletal Muscle Progenitor Differentiation through Phosphatidylinositol 3-Kinase/AKT Signaling.
A. J. Majmundar, N. Skuli, R. C. Mesquita, M. N. Kim, A. G. Yodh, M. Nguyen-McCarty, and M. C. Simon (2012)
Mol. Cell. Biol. 32, 36-49
   Abstract »    Full Text »    PDF »
Drivers of Oxidative Stress in Acute Pancreatitis: The Role of Nutrition Therapy.
S. A. McClave (2012)
JPEN J Parenter Enteral Nutr 36, 24-35
   Abstract »    Full Text »    PDF »
Confronting The Urgent Challenge Of Diabetes: An Overview.
J. E. Fradkin (2012)
Health Aff. 31, 12-19
   Abstract »    Full Text »    PDF »
Endoplasmic Reticulum Stress and Glycogen Synthase Kinase-3{beta} Activation in Apolipoprotein E-Deficient Mouse Models of Accelerated Atherosclerosis.
C. S. McAlpine, A. J. Bowes, M. I. Khan, Y. Shi, and G. H. Werstuck (2012)
Arterioscler Thromb Vasc Biol 32, 82-91
   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 »
Endoplasmic Reticulum Stress Decreases Intracellular Thyroid Hormone Activation via an eIF2a-Mediated Decrease in Type 2 Deiodinase Synthesis.
R. Arrojo e Drigo, T. L. Fonseca, M. Castillo, M. Salathe, G. Simovic, P. Mohacsik, B. Gereben, and A. C. Bianco (2011)
Mol. Endocrinol. 25, 2065-2075
   Abstract »    Full Text »    PDF »
New IBD genetics: common pathways with other diseases.
C. W. Lees, J. C. Barrett, M. Parkes, and J. Satsangi (2011)
Gut 60, 1739-1753
   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 »
SirT1 Regulates Adipose Tissue Inflammation.
M. P. Gillum, M. E. Kotas, D. M. Erion, R. Kursawe, P. Chatterjee, K. T. Nead, E. S. Muise, J. J. Hsiao, D. W. Frederick, S. Yonemitsu, et al. (2011)
Diabetes 60, 3235-3245
   Abstract »    Full Text »    PDF »
Diacerhein Improves Glucose Tolerance and Insulin Sensitivity in Mice on a High-Fat Diet.
N. Tobar, A. G. Oliveira, D. Guadagnini, R. A. Bagarolli, G. Z. Rocha, T. G. Araujo, J. C. Santos-Silva, R. L. Zollner, L. H. B. Boechat, J. B. C. Carvalheira, et al. (2011)
Endocrinology 152, 4080-4093
   Abstract »    Full Text »    PDF »
Crohn's disease: NOD2, autophagy and ER stress converge.
T. Fritz, L. Niederreiter, T. Adolph, R. S. Blumberg, and A. Kaser (2011)
Gut 60, 1580-1588
   Abstract »    Full Text »    PDF »
Influence of the Hepatic Eukaryotic Initiation Factor 2{alpha} (eIF2{alpha}) Endoplasmic Reticulum (ER) Stress Response Pathway on Insulin-mediated ER Stress and Hepatic and Peripheral Glucose Metabolism.
A. L. Birkenfeld, H.-Y. Lee, S. Majumdar, M. J. Jurczak, J. P. Camporez, F. R. Jornayvaz, D. W. Frederick, B. Guigni, M. Kahn, D. Zhang, et al. (2011)
J. Biol. Chem. 286, 36163-36170
   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 (2011)
Gut
   Abstract »    Full Text »
Liver-specific Inducible Nitric-oxide Synthase Expression Is Sufficient to Cause Hepatic Insulin Resistance and Mild Hyperglycemia in Mice.
S. Shinozaki, C. S. Choi, N. Shimizu, M. Yamada, M. Kim, T. Zhang, H. H. Dong, Y.-B. Kim, and M. Kaneki (2011)
J. Biol. Chem. 286, 34959-34975
   Abstract »    Full Text »    PDF »
The Unfolded Protein Response: Integrating Stress Signals Through the Stress Sensor IRE1{alpha}.
C. Hetz, F. Martinon, D. Rodriguez, and L. H. Glimcher (2011)
Physiol Rev 91, 1219-1243
   Abstract »    Full Text »    PDF »
Leptin in human physiology and pathophysiology.
C. S. Mantzoros, F. Magkos, M. Brinkoetter, E. Sienkiewicz, T. A. Dardeno, S.-Y. Kim, O.-P. R. Hamnvik, and A. Koniaris (2011)
Am J Physiol Endocrinol Metab 301, E567-E584
   Abstract »    Full Text »    PDF »
Cellular mechanism of insulin resistance in nonalcoholic fatty liver disease.
N. Kumashiro, D. M. Erion, D. Zhang, M. Kahn, S. A. Beddow, X. Chu, C. D. Still, G. S. Gerhard, X. Han, J. Dziura, et al. (2011)
PNAS 108, 16381-16385
   Abstract »    Full Text »    PDF »
Membrane aberrancy and unfolded proteins activate the endoplasmic reticulum stress sensor Ire1 in different ways.
T. Promlek, Y. Ishiwata-Kimata, M. Shido, M. Sakuramoto, K. Kohno, and Y. Kimata (2011)
Mol. Biol. Cell 22, 3520-3532
   Abstract »    Full Text »    PDF »
Different fatty acids inhibit apoB100 secretion by different pathways: unique roles for ER stress, ceramide, and autophagy.
J. M. Caviglia, C. Gayet, T. Ota, A. Hernandez-Ono, D. M. Conlon, H. Jiang, E. A. Fisher, and H. N. Ginsberg (2011)
J. Lipid Res. 52, 1636-1651
   Abstract »    Full Text »    PDF »
Hepatitis C Virus Infection Promotes Hepatic Gluconeogenesis through an NS5A-Mediated, FoxO1-Dependent Pathway.
L. Deng, I. Shoji, W. Ogawa, S. Kaneda, T. Soga, D.-p. Jiang, Y.-H. Ide, and H. Hotta (2011)
J. Virol. 85, 8556-8568
   Abstract »    Full Text »    PDF »
Developmental exposure to di(2-ethylhexyl) phthalate impairs endocrine pancreas and leads to long-term adverse effects on glucose homeostasis in the rat.
Y. Lin, J. Wei, Y. Li, J. Chen, Z. Zhou, L. Song, Z. Wei, Z. Lv, X. Chen, W. Xia, et al. (2011)
Am J Physiol Endocrinol Metab 301, E527-E538
   Abstract »    Full Text »    PDF »
Mannose-6-phosphate regulates destruction of lipid-linked oligosaccharides.
N. Gao, J. Shang, D. Huynh, V. L. Manthati, C. Arias, H. P. Harding, R. J. Kaufman, I. Mohr, D. Ron, J. R. Falck, et al. (2011)
Mol. Biol. Cell 22, 2994-3009
   Abstract »    Full Text »    PDF »
Subcutaneous administration of leptin normalizes fasting plasma glucose in obese type 2 diabetic UCD-T2DM rats.
B. P. Cummings, A. Bettaieb, J. L. Graham, K. L. Stanhope, R. Dill, G. J. Morton, F. G. Haj, and P. J. Havel (2011)
PNAS 108, 14670-14675
   Abstract »    Full Text »    PDF »
Paracrine and Endocrine Effects of Adipose Tissue on Cancer Development and Progression.
J. Park, D. M. Euhus, and P. E. Scherer (2011)
Endocr. Rev. 32, 550-570
   Abstract »    Full Text »    PDF »
Apoptosis inhibitor of macrophage (AIM) is required for obesity-associated recruitment of inflammatory macrophages into adipose tissue.
J. Kurokawa, H. Nagano, O. Ohara, N. Kubota, T. Kadowaki, S. Arai, and T. Miyazaki (2011)
PNAS 108, 12072-12077
   Abstract »    Full Text »    PDF »
Increased Adipose Tissue Oxygen Tension in Obese Compared With Lean Men Is Accompanied by Insulin Resistance, Impaired Adipose Tissue Capillarization, and Inflammation.
G. H. Goossens, A. Bizzarri, N. Venteclef, Y. Essers, J. P. Cleutjens, E. Konings, J. W. E. Jocken, M. Cajlakovic, V. Ribitsch, K. Clement, et al. (2011)
Circulation 124, 67-76
   Abstract »    Full Text »    PDF »
(n-3) Fatty Acids Alleviate Adipose Tissue Inflammation and Insulin Resistance: Mechanistic Insights.
N. S. Kalupahana, K. J. Claycombe, and N. Moustaid-Moussa (2011)
Adv Nutr 2, 304-316
   PDF »
Endoplasmic Reticulum Oxidoreductin-1-Like {beta} (ERO1l{beta}) Regulates Susceptibility to Endoplasmic Reticulum Stress and Is Induced by Insulin Flux in {beta}-Cells.
C. Khoo, J. Yang, G. Rajpal, Y. Wang, J. Liu, P. Arvan, and D. A. Stoffers (2011)
Endocrinology 152, 2599-2608
   Abstract »    Full Text »    PDF »
Bidirectional Interaction Between Unfolded-Protein-Response Key Protein HSPA5 and Estrogen Signaling in Human Endometrium.
E. Guzel, M. Basar, N. Ocak, A. Arici, and U. A. Kayisli (2011)
Biol Reprod 85, 121-127
   Abstract »    Full Text »    PDF »
Haploid Insufficiency of Suppressor Enhancer Lin12 1-like (SEL1L) Protein Predisposes Mice to High Fat Diet-induced Hyperglycemia.
A. B. Francisco, R. Singh, H. Sha, X. Yan, L. Qi, X. Lei, and Q. Long (2011)
J. Biol. Chem. 286, 22275-22282
   Abstract »    Full Text »    PDF »
Sirtuin 1 (SIRT1) Protein Degradation in Response to Persistent c-Jun N-terminal Kinase 1 (JNK1) Activation Contributes to Hepatic Steatosis in Obesity.
Z. Gao, J. Zhang, I. Kheterpal, N. Kennedy, R. J. Davis, and J. Ye (2011)
J. Biol. Chem. 286, 22227-22234
   Abstract »    Full Text »    PDF »
Constitutive Role for IRE1{alpha}-XBP1 Signaling Pathway in the Insulin-Mediated Hepatic Lipogenic Program.
J. Ning, T. Hong, A. Ward, J. Pi, Z. Liu, H.-Y. Liu, and W. Cao (2011)
Endocrinology 152, 2247-2255
   Abstract »    Full Text »    PDF »
Oleate Blocks Palmitate-Induced Abnormal Lipid Distribution, Endoplasmic Reticulum Expansion and Stress, and Insulin Resistance in Skeletal Muscle.
G. Peng, L. Li, Y. Liu, J. Pu, S. Zhang, J. Yu, J. Zhao, and P. Liu (2011)
Endocrinology 152, 2206-2218
   Abstract »    Full Text »    PDF »
Hepatic steatosis, inflammation, and ER stress in mice maintained long term on a very low-carbohydrate ketogenic diet.
J. R. Garbow, J. M. Doherty, R. C. Schugar, S. Travers, M. L. Weber, A. E. Wentz, N. Ezenwajiaku, D. G. Cotter, E. M. Brunt, and P. A. Crawford (2011)
Am J Physiol Gastrointest Liver Physiol 300, G956-G967
   Abstract »    Full Text »    PDF »
Endoplasmic-Reticulum Calcium Depletion and Disease.
D. Mekahli, G. Bultynck, J. B. Parys, H. De Smedt, and L. Missiaen (2011)
Cold Spring Harb Perspect Biol 3, a004317
   Abstract »    Full Text »    PDF »
Lecithin Cholesterol Acyltransferase Null Mice Are Protected from Diet-induced Obesity and Insulin Resistance in a Gender-specific Manner through Multiple Pathways.
L. Li, M. A. Hossain, S. Sadat, L. Hager, L. Liu, L. Tam, S. Schroer, L. Huogen, I. G. Fantus, P. W. Connelly, et al. (2011)
J. Biol. Chem. 286, 17809-17820
   Abstract »    Full Text »    PDF »
Metabolic Syndrome: Is Nlrp3 Inflammasome a Trigger or a Target of Insulin Resistance?.
M. A. Mori, O. Bezy, and C. R. Kahn (2011)
Circ. Res. 108, 1160-1162
   Full Text »    PDF »
Hepatic overexpression of SIRT1 in mice attenuates endoplasmic reticulum stress and insulin resistance in the liver.
Y. Li, S. Xu, A. Giles, K. Nakamura, J. W. Lee, X. Hou, G. Donmez, J. Li, Z. Luo, K. Walsh, et al. (2011)
FASEB J 25, 1664-1679
   Abstract »    Full Text »    PDF »
The endoplasmic reticulum stress response and diabetic kidney disease.
R. Cunard and K. Sharma (2011)
Am J Physiol Renal Physiol 300, F1054-F1061
   Abstract »    Full Text »    PDF »
Aging as an Event of Proteostasis Collapse.
R. C. Taylor and A. Dillin (2011)
Cold Spring Harb Perspect Biol 3, a004440
   Abstract »    Full Text »    PDF »
Hepatic insulin resistance in mice with hepatic overexpression of diacylglycerol acyltransferase 2.
F. R. Jornayvaz, A. L. Birkenfeld, M. J. Jurczak, S. Kanda, B. A. Guigni, D. C. Jiang, D. Zhang, H.-Y. Lee, V. T. Samuel, and G. I. Shulman (2011)
PNAS 108, 5748-5752
   Abstract »    Full Text »    PDF »
Endoplasmic Reticulum Stress Promotes LIPIN2-Dependent Hepatic Insulin Resistance.
D. Ryu, W.-Y. Seo, Y.-S. Yoon, Y.-N. Kim, S. S. Kim, H.-J. Kim, T.-S. Park, C. S. Choi, and S.-H. Koo (2011)
Diabetes 60, 1072-1081
   Abstract »    Full Text »    PDF »
Mast cells, macrophages, and crown-like structures distinguish subcutaneous from visceral fat in mice.
M. M. Altintas, A. Azad, B. Nayer, G. Contreras, J. Zaias, C. Faul, J. Reiser, and A. Nayer (2011)
J. Lipid Res. 52, 480-488
   Abstract »    Full Text »    PDF »
Troxerutin protects against high cholesterol-induced cognitive deficits in mice.
J. Lu, D.-m. Wu, Z.-h. Zheng, Y.-l. Zheng, B. Hu, and Z.-f. Zhang (2011)
Brain 134, 783-797
   Abstract »    Full Text »    PDF »
Sodium Phenylbutyrate, a Drug With Known Capacity to Reduce Endoplasmic Reticulum Stress, Partially Alleviates Lipid-Induced Insulin Resistance and {beta}-Cell Dysfunction in Humans.
C. Xiao, A. Giacca, and G. F. Lewis (2011)
Diabetes 60, 918-924
   Abstract »    Full Text »    PDF »
Deletion of Nck1 attenuates hepatic ER stress signaling and improves glucose tolerance and insulin signaling in liver of obese mice.
M. Latreille, M.-K. Laberge, G. Bourret, L. Yamani, and L. Larose (2011)
Am J Physiol Endocrinol Metab 300, E423-E434
   Abstract »    Full Text »    PDF »
Adipose tissue transcriptome changes during obesity development in female dogs.
R. W. Grant, B. M. Vester Boler, T. K. Ridge, T. K. Graves, and K. S. Swanson (2011)
Physiol Genomics 43, 295-307
   Abstract »    Full Text »    PDF »
Neural dysregulation of peripheral insulin action and blood pressure by brain endoplasmic reticulum stress.
S. Purkayastha, H. Zhang, G. Zhang, Z. Ahmed, Y. Wang, and D. Cai (2011)
PNAS 108, 2939-2944
   Abstract »    Full Text »    PDF »
Adenylate Kinase 2 Links Mitochondrial Energy Metabolism to the Induction of the Unfolded Protein Response.
A. Burkart, X. Shi, M. Chouinard, and S. Corvera (2011)
J. Biol. Chem. 286, 4081-4089
   Abstract »    Full Text »    PDF »
Preconditioning with Endoplasmic Reticulum Stress Mitigates Retinal Endothelial Inflammation via Activation of X-box Binding Protein 1.
J. Li, J. J. Wang, and S. X. Zhang (2011)
J. Biol. Chem. 286, 4912-4921
   Abstract »    Full Text »    PDF »
Unsaturated FAs prevent palmitate-induced LOX-1 induction via inhibition of ER stress in macrophages.
J. Ishiyama, R. Taguchi, Y. Akasaka, S. Shibata, M. Ito, M. Nagasawa, and K. Murakami (2011)
J. Lipid Res. 52, 299-307
   Abstract »    Full Text »    PDF »
Selective Inactivation of c-Jun NH2-Terminal Kinase in Adipose Tissue Protects Against Diet-Induced Obesity and Improves Insulin Sensitivity in Both Liver and Skeletal Muscle in Mice.
X. Zhang, A. Xu, S. K. Chung, J. H. B. Cresser, G. Sweeney, R. L. C. Wong, A. Lin, and K. S. L. Lam (2011)
Diabetes 60, 486-495
   Abstract »    Full Text »    PDF »
PKC{delta} Is Activated in a Dietary Model of Steatohepatitis and Regulates Endoplasmic Reticulum Stress and Cell Death.
M. W. Greene, C. M. Burrington, M. S. Ruhoff, A. K. Johnson, T. Chongkrairatanakul, and A. Kangwanpornsiri (2010)
J. Biol. Chem. 285, 42115-42129
   Abstract »    Full Text »    PDF »
Sarco(endo)plasmic reticulum Ca2+-ATPase 2b is a major regulator of endoplasmic reticulum stress and glucose homeostasis in obesity.
S. W. Park, Y. Zhou, J. Lee, J. Lee, and U. Ozcan (2010)
PNAS 107, 19320-19325
   Abstract »    Full Text »    PDF »
High-Fat Diet Causes Lipotoxicity Responses in Cumulus-Oocyte Complexes and Decreased Fertilization Rates.
L. L.-Y. Wu, K. R. Dunning, X. Yang, D. L. Russell, M. Lane, R. J. Norman, and R. L. Robker (2010)
Endocrinology 151, 5438-5445
   Abstract »    Full Text »    PDF »
The unfolded protein response is activated in skeletal muscle by high-fat feeding: potential role in the downregulation of protein synthesis.
L. Deldicque, P. D. Cani, A. Philp, J.-M. Raymackers, P. J. Meakin, M. L. J. Ashford, N. M. Delzenne, M. Francaux, and K. Baar (2010)
Am J Physiol Endocrinol Metab 299, E695-E705
   Abstract »    Full Text »    PDF »
An acylic polyisoprenoid derivative, geranylgeranylacetone protects against visceral adiposity and insulin resistance in high-fat-fed mice.
H. Adachi, T. Kondo, R. Ogawa, K. Sasaki, S. Morino-Koga, M. Sakakida, J. Kawashima, H. Motoshima, N. Furukawa, K. Tsuruzoe, et al. (2010)
Am J Physiol Endocrinol Metab 299, E764-E771
   Abstract »    Full Text »    PDF »
DsbA-L Alleviates Endoplasmic Reticulum Stress-Induced Adiponectin Downregulation.
L. Zhou, M. Liu, J. Zhang, H. Chen, L. Q. Dong, and F. Liu (2010)
Diabetes 59, 2809-2816
   Abstract »    Full Text »    PDF »
A Systems Biology Approach Identifies Inflammatory Abnormalities Between Mouse Strains Prior to Development of Metabolic Disease.
M. A. Mori, M. Liu, O. Bezy, K. Almind, H. Shapiro, S. Kasif, and C. R. Kahn (2010)
Diabetes 59, 2960-2971
   Abstract »    Full Text »    PDF »
Endoplasmic Reticulum Stress and Inflammation in Obesity and Diabetes.
S. Hummasti and G. S. Hotamisligil (2010)
Circ. Res. 107, 579-591
   Abstract »    Full Text »    PDF »
Pathologic Changes and Glucose Homeostasis According to Expression of Human Islet Amyloid Polypeptide in Type 2 Diabetic Patients.
J. Y. Park, H. S. No, Y. R. Ahn, S. H. Oh, Y. S. Kim, S. Y. Kim, K. T. Jang, S. W. Kim, J. H. Chung, Y. K. Min, et al. (2010)
Journal of Histochemistry & Cytochemistry 58, 731-740
   Abstract »    Full Text »    PDF »
Distinct gene expression profiles characterize cellular responses to palmitate and oleate.
S. K. Das, A. K. Mondal, and S. C. Elbein (2010)
J. Lipid Res. 51, 2121-2131
   Abstract »    Full Text »    PDF »
FoxO1 Links Hepatic Insulin Action to Endoplasmic Reticulum Stress.
A. Kamagate, D. H. Kim, T. Zhang, S. Slusher, R. Gramignoli, S. C. Strom, S. Bertera, S. Ringquist, and H. H. Dong (2010)
Endocrinology 151, 3521-3535
   Abstract »    Full Text »    PDF »
JNK1 and IKK{beta}: molecular links between obesity and metabolic dysfunction.
G. Solinas and M. Karin (2010)
FASEB J 24, 2596-2611
   Abstract »    Full Text »    PDF »
Intensive Insulin Therapy in Severely Burned Pediatric Patients: A Prospective Randomized Trial.
M. G. Jeschke, G. A. Kulp, R. Kraft, C. C. Finnerty, R. Mlcak, J. O. Lee, and D. N. Herndon (2010)
Am. J. Respir. Crit. Care Med. 182, 351-359
   Abstract »    Full Text »    PDF »
Tauroursodeoxycholic Acid May Improve Liver and Muscle but Not Adipose Tissue Insulin Sensitivity in Obese Men and Women.
M. Kars, L. Yang, M. F. Gregor, B. S. Mohammed, T. A. Pietka, B. N. Finck, B. W. Patterson, J. D. Horton, B. Mittendorfer, G. S. Hotamisligil, et al. (2010)
Diabetes 59, 1899-1905
   Abstract »    Full Text »    PDF »
Mammalian life-span determinant p66shcA mediates obesity-induced insulin resistance.
S. C. Ranieri, S. Fusco, E. Panieri, V. Labate, M. Mele, V. Tesori, A. M. Ferrara, G. Maulucci, M. De Spirito, G. E. Martorana, et al. (2010)
PNAS 107, 13420-13425
   Abstract »    Full Text »    PDF »
Acute Oxidative Stress Can Reverse Insulin Resistance by Inactivation of Cytoplasmic JNK.
A. Berdichevsky, L. Guarente, and A. Bose (2010)
J. Biol. Chem. 285, 21581-21589
   Abstract »    Full Text »    PDF »
Adipose tissue macrophages: their role in adipose tissue remodeling.
T. Suganami and Y. Ogawa (2010)
J. Leukoc. Biol. 88, 33-39
   Abstract »    Full Text »    PDF »
Development of high-fat-diet-induced obesity in female metallothionein-null mice.
M. Sato, T. Kawakami, M. Kondoh, M. Takiguchi, Y. Kadota, S. Himeno, and S. Suzuki (2010)
FASEB J 24, 2375-2384
   Abstract »    Full Text »    PDF »
ER stress and the unfolded protein response in intestinal inflammation.
M. A. McGuckin, R. D. Eri, I. Das, R. Lourie, and T. H. Florin (2010)
Am J Physiol Gastrointest Liver Physiol 298, G820-G832
   Abstract »    Full Text »    PDF »
Activation of AMP-Activated Protein Kinase Inhibits Oxidized LDL-Triggered Endoplasmic Reticulum Stress In Vivo.
Y. Dong, M. Zhang, S. Wang, B. Liang, Z. Zhao, C. Liu, M. Wu, H. C. Choi, T. J. Lyons, and M. H. Zou (2010)
Diabetes 59, 1386-1396
   Abstract »    Full Text »    PDF »
Regulation of basal cellular physiology by the homeostatic unfolded protein response.
D. T. Rutkowski and R. S. Hegde (2010)
J. Cell Biol. 189, 783-794
   Abstract »    Full Text »    PDF »
Linking endoplasmic reticulum stress to cell death in hepatocytes: roles of C/EBP homologous protein and chemical chaperones in palmitate-mediated cell death.
K. T. Pfaffenbach, C. L. Gentile, A. M. Nivala, D. Wang, Y. Wei, and M. J. Pagliassotti (2010)
Am J Physiol Endocrinol Metab 298, E1027-E1035
   Abstract »    Full Text »    PDF »
Rapamycin Inhibits Postprandial-Mediated X-Box-Binding Protein-1 Splicing in Rat Liver.
K. T. Pfaffenbach, A. M. Nivala, L. Reese, F. Ellis, D. Wang, Y. Wei, and M. J. Pagliassotti (2010)
J. Nutr. 140, 879-884
   Abstract »    Full Text »    PDF »
Adipocyte Fatty Acid-binding Protein Modulates Inflammatory Responses in Macrophages through a Positive Feedback Loop Involving c-Jun NH2-terminal Kinases and Activator Protein-1.
X. Hui, H. Li, Z. Zhou, K. S. L. Lam, Y. Xiao, D. Wu, K. Ding, Y. Wang, P. M. Vanhoutte, and A. Xu (2010)
J. Biol. Chem. 285, 10273-10280
   Abstract »    Full Text »    PDF »
Diabetes Mellitus, Inflammation, Obesity: Proposed Treatment Pathways for Current and Future Therapies.
T. E Sonnett, T. L Levien, B. J Gates, J. D Robinson, and R K. Campbell (2010)
Ann. Pharmacother. 44, 701-711
   Abstract »    Full Text »    PDF »
Nitric oxide reduces SLC29A1 promoter activity and adenosine transport involving transcription factor complex hCHOP-C/EBP{alpha} in human umbilical vein endothelial cells from gestational diabetes.
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 »
Relationship Between Functional Promoter Polymorphism in the XBP1 Gene (-116C/G) and Obesity.
E. Yilmaz, M. Berberoglu, and N. Akar (2010)
Clinical and Applied Thrombosis/Hemostasis 16, 99-102
   Abstract »    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.
C. M. Mayer and D. D. Belsham (2010)
Endocrinology 151, 576-585
   Abstract »    Full Text »    PDF »
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.
D. J. Lloyd, M. C. Wheeler, and N. Gekakis (2010)
Diabetes 59, 460-470
   Abstract »    Full Text »    PDF »
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 »

To Advertise     Find Products

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