Cited by 443Adipokines, Inflammation, and Metabolic DiseasesMetabolism, Diabetes, and CancerAdipose Tissue and Metabolism

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Mechanism of Insulin Resistance in A-ZIP/F-1 Fatless Mice

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Kim, Jason K., Gavrilova, Oksana, Chen, Yan, Reitman, Marc L., Shulman, Gerald I.·2000·Journal of Biological Chemistry

DOI 10.1074/jbc.275.12.8456

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Abstract

Insulin resistance is a major factor in the pathogenesis of type 2 diabetes and may be related to alterations in fat metabolism. Fatless mice have been created using dominant-negative protein (A-ZIP/F-1) targeted gene expression in the adipocyte and shown to develop diabetes. To understand the mechanism responsible for the insulin resistance in these mice, we conducted hyperinsulinemic-euglycemic clamps in awake fatless and wild type littermates before the development of diabetes and examined insulin action and signaling in muscle and liver. We found the fatless mice to be severely insulin-resistant, which could be attributed to defects in insulin action in muscle and liver. Both of these abnormalities were associated with defects in insulin activation of insulin receptor substrate-1 and -2-associated phosphatidylinositol 3-kinase activity and a 2-fold increase in muscle and liver triglyceride content. We also show that upon transplantation of fat tissue into these mice, triglyceride content in muscle and liver returned to normal as does insulin signaling and action. In conclusion, these results suggest that the development of insulin resistance in type 2 diabetes may be due to alterations in the partitioning of fat between the adipocyte and muscle/liver leading to accumulation of triglyceride in the latter tissues with subsequent impairment of insulin signaling and action.

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The glucose fatty-acid cycle. Its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus
Randle, P. J., Garland, P. B., Hales, C. N., & Newsholme, E. A. (1963) · The Lancet · doi:10.1016/s0140-6736(63)91500-9 · Cited by 5,093
The Triumvirate: β-Cell, Muscle, Liver: A Collusion Responsible for NIDDM
DeFronzo, R. A. (1988) · Diabetes · doi:10.2337/diab.37.6.667 · Cited by 2,456
Role of Fatty Acids in the Pathogenesis of Insulin Resistance and NIDDM
Boden, G. (1997) · Diabetes · doi:10.2337/diab.46.1.3 · Cited by 1,728
Mechanism of free fatty acid-induced insulin resistance in humans.
Roden, M., Price, T. B., Perseghin, G., Petersen, K. F., Rothman, D. L., Cline, G. W., & Shulman, G. I. (1996) · Journal of Clinical Investigation · doi:10.1172/jci118742 · Cited by 1,539
Self-citation
Effects of free fatty acids on glucose transport and IRS-1–associated phosphatidylinositol 3-kinase activity
Dresner, A., Laurent, D., Marcucci, M., Griffin, M. E., Dufour, S., Cline, G. W., Slezak, L. A., Andersen, D. K., Hundal, R. S., Rothman, D. L., et al. (1999) · Journal of Clinical Investigation · doi:10.1172/jci5001 · Cited by 1,311
Self-citation
Free fatty acid-induced insulin resistance is associated with activation of protein kinase C theta and alterations in the insulin signaling cascade.
Griffin, M. E., Marcucci, M. J., Cline, G. W., Bell, K., Barucci, N., Lee, D., Goodyear, L. J., Kraegen, E. W., White, M. F., & Shulman, G. I. (1999) · Diabetes · doi:10.2337/diabetes.48.6.1270 · Cited by 1,267
Self-citation
Intramyocellular lipid concentrations are correlated with insulin sensitivity in humans: a 1 H NMR spectroscopy study
Krssak, M., Falk Petersen, K., Dresner, A., DiPietro, L., Vogel, S. M., Rothman, D. L., Shulman, G. I., & Roden, M. (1999) · Diabetologia · doi:10.1007/s001250051123 · Cited by 1,264
Self-citation
Skeletal Muscle Triglyceride Levels Are Inversely Related to Insulin Action
Pan, D. A., Lillioja, S., Kriketos, A. D., Milner, M. R., Baur, L. A., Bogardus, C., Jenkins, A. B., & Storlien, L. H. (1997) · Diabetes · doi:10.2337/diab.46.6.983 · Cited by 1,179
Skeletal muscle triglyceride levels are inversely related to insulin action
Pan, D. A., Lillioja, S., Kriketos, A. D., Milner, M. R., Baur, L. A., Bogardus, C., Jenkins, A. B., & Storlien, L. H. (1997) · Diabetes · doi:10.2337/diabetes.46.6.983 · Cited by 1,179
Leptin reverses insulin resistance and diabetes mellitus in mice with congenital lipodystrophy
Shimomura, I., Hammer, R. E., Ikemoto, S., Brown, M. S., & Goldstein, J. L. (1999) · Nature · doi:10.1038/43448 · Cited by 1,038

Show all 30 references

Research works printed but not linked: 2

Ohshima, 1984, Am. J. Physiol., 246, E193
Previs, 1999, Diabetes, 48, A51

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Deng, T., Shan, S., Li, P., Shen, Z.-F., Lu, X.-P., Cheng, J., & Ning, Z.-Q. (2005) · Endocrinology · doi:10.1210/en.2005-0623 · Cited by 90
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Zammouri, J., Vatier, C., Capel, É., Auclair, M., Storey, C., Bismuth, É., Mosbah, H., Donadille, B., Janmaat, S., Fève, B., et al. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.803189 · Cited by 95
New insights into the pathogenesis of insulin resistance in humans using magnetic resonance spectroscopy
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Monocyte chemoattractant protein-1 (MCP-1) deficiency enhances alternatively activated M2 macrophages and ameliorates insulin resistance and fatty liver in lipoatrophic diabetic A-ZIP transgenic mice
Nio, Y., Yamauchi, T., Iwabu, M., Okada‐Iwabu, M., Funata, M., Yamaguchi, M., Ueki, K., & Kadowaki, T. (2012) · Diabetologia · doi:10.1007/s00125-012-2710-2 · Cited by 86
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Akhtar, D. H., Iqbal, U., Vazquez‐Montesino, L. M., Dennis, B. B., & Ahmed, A. (2019) · Journal of Clinical and Translational Hepatology · doi:10.14218/jcth.2019.00028 · Cited by 89
Letting lipids go: hormone-sensitive lipase
Haemmerle, G., Zimmermann, R., & Zechner, R. (2003) · Current Opinion in Lipidology · doi:10.1097/00041433-200306000-00009 · Cited by 87
Doxorubicin treatment inhibits PPARγ and may induce lipotoxicity by mimicking a type 2 diabetes‐like condition in rodent models
Arunachalam, S., Pichiah, P. B. T., & Achiraman, S. (2012) · FEBS Letters · doi:10.1016/j.febslet.2012.11.019 · Cited by 90
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Xie, J. T., Wu, J., Mehendale, S. R., Aung, H. H., & Yuan, C. (2004) · Phytomedicine · doi:10.1078/0944-7113-00325 · Cited by 84
Human 1-Acylglycerol-3-phosphate O-Acyltransferase Isoforms 1 and 2
Agarwal, A. K., Sukumaran, S., Cortés, V., Tunison, K., Mizrachi, D., Sankella, S., Gerard, R. D., Horton, J. D., & Garg, A. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.250449 · Cited by 84
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Self-citation
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Morrison, C. D., Huypens, P., Stewart, L. K., & Gettys, T. W. (2008) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2008.09.005 · Cited by 83
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Geisler, J. G., Zawalich, W. S., Zawalich, K. C., Lakey, J. R. T., Stukenbrok, H., Milici, A. J., & Soeller, W. C. (2002) · Diabetes · doi:10.2337/diabetes.51.7.2158 · Cited by 79
Skeletal Muscle Metabolic Dysfunction in Obesity and Metabolic Syndrome
Wells, G. D., Noseworthy, M. D., Hamilton, J. K., Tarnopolski, M., & Tein, I. (2008) · Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques · doi:10.1017/s0317167100007538 · Cited by 79
M ETABOLIC L ESSONS FROM G ENETICALLY L EAN M ICE
Reitman, M. L. (2002) · Annual Review of Nutrition · doi:10.1146/annurev.nutr.22.010402.102849 · Cited by 75
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Xia, Z., Stanhope, K. L., Digitale, E., Simion, O.-M., Chen, L., Havel, P. J., & Cianflone, K. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m311319200 · Cited by 75
Effects of introducing physical training in the course of a 16-week high-fat diet regimen on hepatic steatosis, adipose tissue fat accumulation, and plasma lipid profile
Gauthier, M.-S., Couturier, K., Charbonneau, A., & Lavoie, J.-M. (2004) · International Journal of Obesity · doi:10.1038/sj.ijo.0802628 · Cited by 76
Pharmacotherapy of obesity: targets and perspectives
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Shafrir, E., & Raz, I. (2003) · Diabetologia · doi:10.1007/s00125-003-1052-5 · Cited by 75
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Role of energy charge and AMP-activated protein kinase in adipocytes in the control of body fat stores
Rossmeisl, M., Flachs, P., Brauner, P., Sponarova, J., Matejkova, O., Prazak, T., Ruzickova, J., Bardova, K., Kuda, O., & Kopecky, J. (2004) · International Journal of Obesity · doi:10.1038/sj.ijo.0802855 · Cited by 71
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Shin, M., Yao, Q., Jun, J. C., Bevans‐Fonti, S., Yoo, D.-Y., Han, W., Mesarwi, O. A., Richardson, R., Fu, Y., Pasricha, P. J., et al. (2014) · Journal of Applied Physiology · doi:10.1152/japplphysiol.01133.2013 · Cited by 71
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Perseghin, G., Scifo, P., Danna, M., Battezzati, A., Benedini, S., Meneghini, E., Maschio, A. D., & Luzi, L. (2002) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00127.2002 · Cited by 69
Loss of protein kinase Cβ function protects mice against diet-induced obesity and development of hepatic steatosis and insulin resistance #
Huang, W., Bansode, R. R., Mehta, M., & Mehta, K. D. (2008) · Hepatology · doi:10.1002/hep.22815 · Cited by 68
Failure of dietary quercetin to alter the temporal progression of insulin resistance among tissues of C57BL/6J mice during the development of diet-induced obesity
Stewart, L. K., Wang, Z., Ribnicky, D., Soileau, J. L., Cefalu, W. T., & Gettys, T. W. (2009) · Diabetologia · doi:10.1007/s00125-008-1252-0 · Cited by 71
Myostatin Inhibition Prevents Diabetes and Hyperphagia in a Mouse Model of Lipodystrophy
Guo, T., Bond, N. D., Jou, W., Gavrilova, O., Portas, J., & McPherron, A. C. (2012) · Diabetes · doi:10.2337/db11-0915 · Cited by 68
Self-citation
Non-Invasive Quantification of White and Brown Adipose Tissues and Liver Fat Content by Computed Tomography in Mice
Lubura, M., Hesse, D., Neumann, N., Scherneck, S., Wiedmer, P., & Schürmann, A. (2012) · PLoS ONE · doi:10.1371/journal.pone.0037026 · Cited by 69
Systems-level analysis of insulin action in mouse strains provides insight into tissue- and pathway-specific interactions that drive insulin resistance
Nelson, M. E., Madsen, S., Cooke, K. C., Fritzen, A. M., Thorius, I. H., Masson, S. W. C., Carroll, L., Weiss, F. C., Seldin, M. M., Potter, M., et al. (2022) · Cell Metabolism · doi:10.1016/j.cmet.2021.12.013 · Cited by 61
Bone marrow adipose tissue as an endocrine organ: close to the bone?
Sulston, R. J., & Cawthorn, W. P. (2016) · Hormone Molecular Biology and Clinical Investigation · doi:10.1515/hmbci-2016-0012 · Cited by 67
Syntaxin 4 Transgenic Mice Exhibit Enhanced Insulin-Mediated Glucose Uptake in Skeletal Muscle
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Authors: Kim, J. K., Gavrilova, O., Chen, Y., Reitman, M. L., & Shulman, G. I.
Affiliations: Howard Hughes Medical Institute (US)
National Institutes of Health (US)
Corresponding author: Shulman, Gerald I.
ORCID: Kim, Jason K.
Gavrilova, Oksana
Reitman, Marc L.
Shulman, Gerald I.
Venue: Journal of Biological Chemistry
Publisher: Elsevier BV
Published: 2000-03
Volume: 275
Issue: 12
Pages: 8456-8460
ISSN: 0021-9258 (ISSN-L)
DOI: 10.1074/jbc.275.12.8456
OpenAlex: W2111445543
Cited by: 443
References: 30
Citations by year: 2026: 3 · 2025: 3 · 2024: 7 · 2023: 4 · 2022: 8 · 2021: 13 · 2020: 12 · 2019: 15 · 2018: 10 · 2017: 19 · 2016: 18 · 2015: 18 · 2014: 14 · 2013: 19 · 2012: 17
FWCI: 25.12
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
creativecommons.org/licenses/by/4.0/ (vor, 7526 d)
Locations: Journal of Biological Chemistry (publishedVersion, cc-by)
PubMed (publishedVersion)
Funders: Eli Lilly and Company
National Institute of Diabetes and Digestive and Kidney Diseases (P30DK45735, R01-DK40936, R01DK040936, P30DK045735)
Topics: Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
Keywords: insulin resistance, type 2 diabetes, IRS-1, insulin receptor substrate 2, phosphatidylinositol 3-kinase, insulin signaling, liver triglyceride accumulation, fat partitioning, fat transplantation, hyperinsulinemic-euglycemic clamp
MeSH terms: Adipose Tissue, Animals, Body Composition, Insulin, Insulin Resistance, Liver, Mice, Mutant Strains, Mice, Transgenic, Muscles, Phosphoproteins, Transcription Factors, Glucose Clamp Technique, Phosphatidylinositol 3-Kinases, Intracellular Signaling Peptides and Proteins, Mice, Insulin Receptor Substrate Proteins

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Mechanism of Insulin Resistance in A-ZIP/F-1 Fatless Mice

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