Cited by 500Metabolism, Diabetes, and CancerDiabetes, Cardiovascular Risks, and LipoproteinsAdipokines, Inflammation, and Metabolic Diseases

The DOI matches its Crossref record; 33 of the 33 references it cites were found in a registry or an index.

PKC-θ knockout mice are protected from fat-induced insulin resistance

Open access

Kim, Jason K., Fillmore, Jonathan J., Sunshine, Mary Jean, Albrecht, Bjoern, Higashimori, Takamasa, Kim, Dong-Wook, Liu, Zhen-Xiang, Soos, Timothy J., Cline, Gary W., O’Brien, William R., Littman, Dan R., Shulman, Gerald I.·2004·Journal of Clinical Investigation

DOI 10.1172/jci200422230PMC PMC516267

Open this paper in CoChat — free account Open PDF

Abstract

Insulin resistance plays a primary role in the development of type 2 diabetes and may be related to alterations in fat metabolism. Recent studies have suggested that local accumulation of fat metabolites inside skeletal muscle may activate a serine kinase cascade involving protein kinase C–θ (PKC-θ), leading to defects in insulin signaling and glucose transport in skeletal muscle. To test this hypothesis, we examined whether mice with inactivation of PKC-θ are protected from fat-induced insulin resistance in skeletal muscle. Skeletal muscle and hepatic insulin action as assessed during hyperinsulinemic-euglycemic clamps did not differ between WT and PKC-θ KO mice following saline infusion. A 5-hour lipid infusion decreased insulin-stimulated skeletal muscle glucose uptake in the WT mice that was associated with 40–50% decreases in insulin-stimulated tyrosine phosphorylation of insulin receptor substrate–1 (IRS-1) and IRS-1–associated PI3K activity. In contrast, PKC-θ inactivation prevented fat-induced defects in insulin signaling and glucose transport in skeletal muscle. In conclusion, our findings demonstrate that PKC-θ is a crucial component mediating fat-induced insulin resistance in skeletal muscle and suggest that PKC-θ is a potential therapeutic target for the treatment of type 2 diabetes.

Integrity signals

Registry

Crossref · 10.1172/jci200422230

Cites

33 of 33 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

We couldn’t retrieve this paper’s full text, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Cellular mechanisms of insulin resistance
Shulman, G. I. (2000) · Journal of Clinical Investigation · doi:10.1172/jci10583 · Cited by 2,714
Self-citation
Mechanism by Which Fatty Acids Inhibit Insulin Activation of Insulin Receptor Substrate-1 (IRS-1)-associated Phosphatidylinositol 3-Kinase Activity in Muscle
Yu, C., Chen, Y., Cline, G. W., Zhang, D., Zong, H., Wang, Y., Bergeron, R., Kim, J. K., Cushman, S. W., Cooney, G. J., et al. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m200958200 · Cited by 1,561
Self-citation
Lipid-Induced Insulin Resistance in Human Muscle Is Associated With Changes in Diacylglycerol, Protein Kinase C, and IκB-α
Itani, S. I., Ruderman, N. B., Schmieder, F., & Boden, G. (2002) · Diabetes · doi:10.2337/diabetes.51.7.2005 · Cited by 1,390
Free fatty acids in obesity and type 2 diabetes: defining their role in the development of insulin resistance and β‐cell dysfunction
Boden, G., & Shulman, G. I. (2002) · European Journal of Clinical Investigation · doi:10.1046/j.1365-2362.32.s3.3.x · Cited by 1,300
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
Quantitation of Muscle Glycogen Synthesis in Normal Subjects and Subjects with Non-Insulin-Dependent Diabetes by13C Nuclear Magnetic Resonance Spectroscopy
Shulman, G. I., Rothman, D. L., Jue, T., Stein, P., DeFronzo, R. A., & Shulman, R. G. (1990) · New England Journal of Medicine · doi:10.1056/nejm199001253220403 · Cited by 1,248
Self-citation
Slow glucose removal rate and hyperinsulinemia precede the development of type II diabetes in the offspring of diabetic parents
Warram, J. H., Martin, B. C., Krolewski, A. S., Soeldner, J. S., & Kahn, C. R. (1990) · Annals of Internal Medicine · doi:10.7326/0003-4819-113-12-909 · Cited by 1,038
Insulin Action, Diabetogenes, and the Cause of Type II Diabetes
Kahn, C. R. (1994) · Diabetes · doi:10.2337/diab.43.8.1066 · Cited by 916
PKC-θ is required for TCR-induced NF-κB activation in mature but not immature T lymphocytes
Sun, Z., Arendt, C., Ellmeier, W., Schaeffer, E. M., Sunshine, M. J., Gandhi, L., Annes, J. P., Petrzilka, D., Kupfer, A., Schwartzberg, P. L., et al. (2000) · Nature · doi:10.1038/35006090 · Cited by 894
Self-citation
Tissue-specific overexpression of lipoprotein lipase causes tissue-specific insulin resistance
Kim, J. K., Fillmore, J. J., Chen, Y., Yu, C., Moore, I. K., Pypaert, M., Lutz, E. P., Kako, Y., Velez-Carrasco, W., Goldberg, I. J., et al. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.121164498 · Cited by 753
Self-citation

Show all 31 references

Research works printed but not linked: 1

Shaw, 2000, Diabetes Care., 23(Suppl. 2), B5

Sorted by citations

Items 201–300 of 499

Insulin Resistance, Obesity, and Lipotoxicity
Yazıcı, D., Demir, S. Ç., & Sezer, H. (2024) · Advances in experimental medicine and biology · doi:10.1007/978-3-031-63657-8_14 · Cited by 85
Resveratrol inhibits insulin secretion from rat pancreatic islets
Szkudelski, T. (2006) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2006.09.046 · Cited by 71
Skeletal intramyocellular lipid metabolism and insulin resistance
Li, Y., Xu, S., Zhang, X., Yi, Z.-C., & Cichello, S. A. (2015) · Biophysics Reports · doi:10.1007/s41048-015-0013-0 · Cited by 74
Silibinin improves palmitate-induced insulin resistance in C2C12 myotubes by attenuating IRS-1/PI3K/Akt pathway inhibition
Li, H. B., Yang, Y., Mo, Z. J., Ding, Y.-B., & Jiang, W. (2015) · Brazilian Journal of Medical and Biological Research · doi:10.1590/1414-431x20144238 · Cited by 69
Regulation of ER stress-induced macroautophagy by protein kinase C
Sakaki, K., & Kaufman, R. J. (2008) · Autophagy · doi:10.4161/auto.6607 · Cited by 69
Cellular inflammatory responses: Novel insights for obesity and insulin resistance
Chen, H. (2006) · Pharmacological Research · doi:10.1016/j.phrs.2006.03.003 · Cited by 68
Acute hepatic steatosis in mice by blocking β-oxidation does not reduce insulin sensitivity of very-low-density lipoprotein production
Grefhorst, A., Hoekstra, J., Derks, T. G. J., Ouwens, D. M., Baller, J. F. W., Havinga, R., Havekes, L. M., Romijn, J. A., & Kuipers, F. (2005) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00063.2005 · Cited by 68
Inactivation of PKCθ leads to increased susceptibility to obesity and dietary insulin resistance in mice
Gao, Z., Wang, Z., Zhang, X., Butler, A. A., Zuberi, A. R., Gawrońska‐Kozak, B., Lefevre, M., York, D., Ravussin, É., Berthoud, H., et al. (2006) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00178.2006 · Cited by 66
Mechanism by which arylamine N -acetyltransferase 1 ablation causes insulin resistance in mice
Camporez, J. P., Wang, Y., Faarkrog, K., Chukijrungroat, N., Petersen, K. F., & Shulman, G. I. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1716990115 · Cited by 67
Self-citation
Hyperglycemia, maturity-onset obesity, and insulin resistance in NONcNZO10/LtJ males, a new mouse model of type 2 diabetes
Cho, Y.-R., Kim, H., Park, S., Ko, H. J., Hong, E., Higashimori, T., Zhang, Z., Jung, D. Y., Ola, M. S., LaNoue, K. F., et al. (2007) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00376.2006 · Cited by 63
Self-citation
Diabetic cardiomyopathy: signaling defects and therapeutic approaches
Dobrin, J. S., & Lebeche, D. (2010) · Expert Review of Cardiovascular Therapy · doi:10.1586/erc.10.17 · Cited by 63
Insulin Resistance and Cardiovascular Risk: New Insights From Molecular and Cellular Biology
Morisco, C., Lembo, G., & Trimarco, B. (2006) · Trends in Cardiovascular Medicine · doi:10.1016/j.tcm.2006.03.008 · Cited by 65
Metabolic crossroads in insulin resistance: exploring lipid dysregulation and inflammation
Saadati, S., Godini, R., Reddy, A. J., Teede, H. J., & Mousa, A. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1692742 · Cited by 71
Protein Kinase C θ Activation Induces Insulin-Mediated Constriction of Muscle Resistance Arteries
Bakker, W., Sipkema, P., Stehouwer, C. D. A., Serné, E. H., Smulders, Y. M., van Hinsbergh, V. W. M., & Eringa, E. C. (2007) · Diabetes · doi:10.2337/db07-0792 · Cited by 62
The regulation of food intake by insulin in the central nervous system
Mitchell, C. S., & Begg, D. P. (2021) · Journal of Neuroendocrinology · doi:10.1111/jne.12952 · Cited by 62
Diverse roles for protein kinase C δ and protein kinase C ε in the generation of high-fat-diet-induced glucose intolerance in mice: regulation of lipogenesis by protein kinase C δ
Frangioudakis, G., Burchfield, J. G., Narasimhan, S. R., Cooney, G. J., Leitges, M., Biden, T. J., & Schmitz‐Peiffer, C. (2009) · Diabetologia · doi:10.1007/s00125-009-1543-0 · Cited by 59
Palmitate-Activated Macrophages Confer Insulin Resistance to Muscle Cells by a Mechanism Involving Protein Kinase C θ and ε
Kewalramani, G., Fink, L. N., Asadi, F., & Klip, A. (2011) · PLoS ONE · doi:10.1371/journal.pone.0026947 · Cited by 57
Chapter 13 Phosphorylation of IRS Proteins
Sun, X., & Liu, F. (2009) · Vitamins and hormones · doi:10.1016/s0083-6729(08)00613-4 · Cited by 57
Protein Kinase Cθ Via Activating Transcription Factor 2-Mediated CD36 Expression and Foam Cell Formation of Ly6C hi Cells Contributes to Atherosclerosis
Raghavan, S., Singh, N. K., Gali, S., Mani, A. M., & Rao, G. N. (2018) · Circulation · doi:10.1161/circulationaha.118.034083 · Cited by 56
High-fat diet action on adiposity, inflammation, and insulin sensitivity depends on the control low-fat diet
Benoit, B., Plaisancié, P., Awada, M., Géloën, A., Estienne, M., Capel, F., Malpuech‐Brugère, C., Debard, C., Pesenti, S., Morio, B., et al. (2013) · Nutrition Research · doi:10.1016/j.nutres.2013.07.017 · Cited by 55
PPARβ/δ and lipid metabolism in the heart
Palomer, X., Barroso, E., Zarei, M., Botteri, G., & Vázquez‐Carrera, M. (2016) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2016.01.019 · Cited by 58
The Yin and Yang of Protein Kinase C-theta (PKCθ)
Zhang, E. Y., Kong, K., & Altman, A. (2013) · Advances in pharmacology · doi:10.1016/b978-0-12-404717-4.00006-8 · Cited by 58
Skeletal muscle glucose metabolism and inflammation in the development of the metabolic syndrome
Marette, A., Liu, Y., & Sweeney, G. (2014) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-014-9296-6 · Cited by 55
Mechanistic insight into high-fat diet-induced metabolic inflammation in the arcuate nucleus of the hypothalamus
Ullah, R., Rauf, N., Nabi, G., Shen, Y., Yu-Dong, Z., & Fu, J. (2021) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2021.112012 · Cited by 64
Mechanism of glucose intolerance in mice with dominant negative mutation of CEACAM1
Park, S.-Y., Cho, Y.-R., Kim, H.-J., Hong, E.-G., Higashimori, T., Lee, S. J., Goldberg, I. J., Shulman, G. I., Najjar, S. M., & Kim, J. K. (2006) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00077.2006 · Cited by 51
Self-citation
Perspectives and Potential Applications of Mitochondria‐Targeted Antioxidants in Cardiometabolic Diseases and Type 2 Diabetes
Rocha, M., Apostolova, N., Herance, J. R., Rovira‐Llopis, S., Hernández‐Mijares, A., & Víctor, V. M. (2013) · Medicinal Research Reviews · doi:10.1002/med.21285 · Cited by 51
Mulberry leaf tea alleviates diabetic nephropathy by inhibiting PKC signaling and modulating intestinal flora
Sheng, Y., Zheng, S., Zhang, C., Zhao, C., He, X., Xu, W., & Huang, K. (2018) · Journal of Functional Foods · doi:10.1016/j.jff.2018.04.040 · Cited by 51
Ciliary Neurotrophic Factor Stimulates Muscle Glucose Uptake by a PI3-Kinase–Dependent Pathway That Is Impaired With Obesity
Steinberg, G. R., Watt, M. J., Ernst, M., Birnbaum, M. J., Kemp, B. E., & Jørgensen, S. B. (2009) · Diabetes · doi:10.2337/db08-0659 · Cited by 54
Raspberry Supplementation Improves Insulin Signaling and Promotes Brown‐Like Adipocyte Development in White Adipose Tissue of Obese Mice
Xing, T., Kang, Y., Xu, X., Wang, B., Du, ‬., & Zhu, M. J. (2018) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201701035 · Cited by 50
STORING UP TROUBLE: DOES ACCUMULATION OF INTRAMYOCELLULAR TRIGLYCERIDE PROTECT SKELETAL MUSCLE FROM INSULIN RESISTANCE?
Watt, M. J. (2008) · Clinical and Experimental Pharmacology and Physiology · doi:10.1111/j.1440-1681.2008.05075.x · Cited by 50
PKCδ-mediated IRS-1 Ser24 phosphorylation negatively regulates IRS-1 function
Greene, M. W., Ruhoff, M. S., Roth, R. A., Kim, J., Quon, M. J., & Krause, J. A. (2006) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2006.08.158 · Cited by 48
Self-citation
Genetic Analysis of the Role of Protein Kinase Cθ in Platelet Function and Thrombus Formation
Hall, K. J., Harper, M. T., Gilio, K., Cosemans, J. M. E. M., Heemskerk, J. W. M., & Poole, A. W. (2008) · PLoS ONE · doi:10.1371/journal.pone.0003277 · Cited by 48
Short-term weight loss attenuates local tissue inflammation and improves insulin sensitivity without affecting adipose inflammation in obese mice
Jung, D. Y., Ko, H. J., Lichtman, E. I., Lee, E., Lawton, E., Ong, H., Yu, K., Azuma, Y., Friedline, R. H., Lee, K. W., et al. (2013) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00462.2012 · Cited by 48
Self-citation
Effect of Diabetes on Alteration of Metabolism in Cardiac Myocytes: Therapeutic Implications
Kota, S. K., Kota, S. K., Jammula, S., Panda, S. K., & Modi, K. D. (2011) · Diabetes Technology & Therapeutics · doi:10.1089/dia.2011.0120 · Cited by 47
Substance P (SP)-Neurokinin-1 Receptor (NK-1R) Alters Adipose Tissue Responses to High-Fat Diet and Insulin Action
Karagiannides, I., Stavrakis, D. G., Bakirtzi, K., Kokkotou, E. G., Pirtskhalava, T., Nayeb‐Hashemi, H., Bowe, C., Bugni, J. M., Nuño, M., Lu, B., et al. (2011) · Endocrinology · doi:10.1210/en.2010-1345 · Cited by 46
High-fat feeding increases insulin receptor and IRS-1 coimmunoprecipitation with SOCS-3, IKKα/β phosphorylation and decreases PI-3 kinase activity in muscle
Yaspelkis, B. B., Kvasha, I. A., & Figueroa, T. Y. (2009) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00117.2009 · Cited by 48
IRS posttranslational modifications in regulating insulin signaling
Peng, J., & He, L. (2017) · Journal of Molecular Endocrinology · doi:10.1530/jme-17-0151 · Cited by 49
Leptin, skeletal muscle lipids, and lipid-induced insulin resistance
Dubé, J. J., Bhatt, B. A., Dedousis, N., Bonen, A., & O'Doherty, R. M. (2007) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00133.2007 · Cited by 47
Chapter 12 Serine Kinases of Insulin Receptor Substrate Proteins
Boura‐Halfon, S., & Zick, Y. (2009) · Vitamins and hormones · doi:10.1016/s0083-6729(08)00612-2 · Cited by 53
The tail wagging the dog – regulation of lipid metabolism by protein kinase C
Schmitz‐Peiffer, C. (2013) · FEBS Journal · doi:10.1111/febs.12285 · Cited by 47
PKCθ is a key player in the development of insulin resistance
Haasch, D. L., Berg, C. E., Clampit, J. E., Pederson, T. M., Frost, L., Kroeger, P., & Rondinone, C. M. (2006) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2006.02.177 · Cited by 46
Lipid metabolism disturbances contribute to insulin resistance and decrease insulin sensitivity by malathion exposure in Wistar rat
Lasram, M. M., Bouzid, K., Douib, I. B., Annabi, A. B., Elj, N. E., Fazâa, S. E., Abdelmoula, J., & Gharbi, N. (2014) · Drug and Chemical Toxicology · doi:10.3109/01480545.2014.933348 · Cited by 46
Diabetes-related metabolic perturbations in cardiac myocyte
Feuvray, D., & Darmellah, A. (2008) · Diabetes & Metabolism · doi:10.1016/s1262-3636(08)70096-x · Cited by 45
Lipocalin 13 protein protects against hepatic steatosis by both inhibiting lipogenesis and stimulating fatty acid β-oxidation
Sheng, L., Cho, K. W., Zhou, Y., Shen, H., & Rui, L. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.256677 · Cited by 45
Mechanisms and Active Compounds Polysaccharides and Bibenzyls of Medicinal Dendrobiums for Diabetes Management
Li, M., Trapika, I. G. M. G. S. C., Tang, S. Y. S., Cho, J., Qi, Y., Li, C. G., Li, Y., Yao, M., Yang, D., Liu, B., et al. (2022) · Frontiers in Nutrition · doi:10.3389/fnut.2021.811870 · Cited by 45
Deciphering the complex interplay of risk factors in type 2 diabetes mellitus: A comprehensive review
Singh, S., Kriti, M., Anamika, K. S., Sarma, D. K., Verma, V., Nagpal, R., Mohania, D., Tiwari, R. R., & Kumar, M. (2024) · Metabolism Open · doi:10.1016/j.metop.2024.100287 · Cited by 56
Human mitochondrial oxidative capacity is acutely impaired after burn trauma
Cree‐Green, M., Fram, R. Y., Herndon, D. N., Qian, T., Angel, C. A., Green, J. M., Mlcak, R. P., Aarsland, A. A., & Wolfe, R. R. (2008) · The American Journal of Surgery · doi:10.1016/j.amjsurg.2007.09.048 · Cited by 43
Krüppel-like factor (KLF)5: An emerging foe of cardiovascular health
Palioura, D., Lazou, A., & Drosatos, K. (2021) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2021.10.002 · Cited by 45
Phosphorylation of Ser357 of Rat Insulin Receptor Substrate-1 Mediates Adverse Effects of Protein Kinase C-δ on Insulin Action in Skeletal Muscle Cells
Waraich, R. S., Weigert, C., Kalbacher, H., Hennige, A. M., Lutz, S. Z., Häring, H., Schleicher, E. D., Voelter, W., & Lehmann, R. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m708588200 · Cited by 43
Reduced AMP-activated protein kinase activity in mouse skeletal muscle does not exacerbate the development of insulin resistance with obesity
Beck Jørgensen, S., O’Neill, H. M., Hewitt, K., Kemp, B. E., & Steinberg, G. R. (2009) · Diabetologia · doi:10.1007/s00125-009-1483-8 · Cited by 42
Mcl-1 Degradation during Hepatocyte Lipoapoptosis
Masuoka, H. C., Mott, J. L., Bronk, S. F., Werneburg, N. W., Akazawa, Y., Kaufmann, S. H., & Gores, G. J. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.039545 · Cited by 42
Dietary palmitate and oleate differently modulate insulin sensitivity in human skeletal muscle
Sarabhai, T., Koliaki, C. C., Mastrototaro, L., KAHL, S., Pesta, D. H., Apostolopoulou, M., Wolkersdorfer, M. F., Bönner, A. C., Bobrov, P., Markgraf, D. F., et al. (2021) · Diabetologia · doi:10.1007/s00125-021-05596-z · Cited by 42
Muscle-specific Knock-out of NUAK Family SNF1-like Kinase 1 (NUAK1) Prevents High Fat Diet-induced Glucose Intolerance
Inazuka, F., Sugiyama, N., Tomita, M., Abe, T., Shioi, G., & Esumi, H. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.302687 · Cited by 43
Epigenetic regulation of inflammation in insulin resistance
Klimczak, S., & Śliwińska, A. (2022) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2022.09.004 · Cited by 47
High-fat load: mechanism(s) of insulin resistance in skeletal muscle
Lark, D. S., Fisher‐Wellman, K. H., & Neufer, P. D. (2012) · International Journal of Obesity Supplements · doi:10.1038/ijosup.2012.20 · Cited by 41
The role of protein kinases as key drivers of metabolic dysfunction-associated fatty liver disease progression: New insights and future directions
Alshehade, S. A., Alshawsh, M. A., Murugaiyah, V., Asif, M., Alshehade, O., Almoustafa, H. A., & Zarzour, R. H. A. (2022) · Life Sciences · doi:10.1016/j.lfs.2022.120732 · Cited by 42
Molecular Mechanisms of Insulin Resistance Development
Va, T., & Vorotnikov, A. V. (2014) · Diabetes Mellitus · doi:10.14341/dm2014229-40 · Cited by 48
PEDF-induced alteration of metabolism leading to insulin resistance
Carnagarin, R., Dharmarajan, A., & Dass, C. R. (2014) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2014.11.006 · Cited by 41
MondoA drives muscle lipid accumulation and insulin resistance
Ahn, B. Y., Wan, S., Jaiswal, N., Vega, R. B., Ayer, D. E., Titchenell, P. M., Han, X., Won, K., & Kelly, D. P. (2019) · JCI Insight · doi:10.1172/jci.insight.129119 · Cited by 40
Protectin DX ameliorates palmitate- or high-fat diet-induced insulin resistance and inflammation through an AMPK-PPARα-dependent pathway in mice
Jung, T. W., Kim, H., El‐Aty, A. M. A., & Jeong, J. H. (2017) · Scientific Reports · doi:10.1038/s41598-017-01603-9 · Cited by 40
Berberine treatment attenuates the palmitate-mediated inhibition of glucose uptake and consumption through increased 1,2,3-triacyl-sn-glycerol synthesis and accumulation in H9c2 cardiomyocytes
Chang, W., Chen, L., & Hatch, G. M. (2016) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2015.12.017 · Cited by 38
Inhibitory effect on protein kinase Cθ by Crocetin attenuates palmitate-induced insulin insensitivity in 3T3-L1 adipocytes
Yang, L., Qian, Z., Ji, H., Yang, R., Wang, Y., Liang, X., Sheng, L., Zhao, B., & Zhang, X. (2010) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2010.05.061 · Cited by 38
Phosphorylation of Irs1 at SER-522 Inhibits Insulin Signaling
Giraud, J., Haas, M., Feener, E. P., Copps, K. D., Dong, X. C., Dunn, S. L., & White, M. F. (2007) · Molecular Endocrinology · doi:10.1210/me.2007-0159 · Cited by 38
Insights into the development of insulin resistance: Unraveling the interaction of physical inactivity, lipid metabolism and mitochondrial biology
Handy, R. M., & Holloway, G. P. (2023) · Frontiers in Physiology · doi:10.3389/fphys.2023.1151389 · Cited by 38
“The importance of DAG-mediated PKC activation in this pathway has been evidenced with the ablation of PKC-θ in murine skeletal muscle which protects mice from high-fat dietinduced insulin resistance (Kim et al., 2004), as does muscle-specific alanine substitutions on IRS-1 at various serine phosphorylation sites (Mori…”
Background
The Novel PKCθfrom Benchtop to Clinic
Hage‐Sleiman, R., Hamze, A. B., Reslan, L., Kobeissy, H., & Dbaibo, G. S. (2015) · Journal of Immunology Research · doi:10.1155/2015/348798 · Cited by 38
Systemic Effects of White Adipose Tissue Dysregulation and Obesity‐Related Inflammation
Guri, A. J., & Bassaganya-Riera, J. (2010) · Obesity · doi:10.1038/oby.2010.230 · Cited by 37
Role of Substance P in the Regulation of Glucose Metabolism via Insulin Signaling-Associated Pathways
Karagiannides, I., Bakirtzi, K., Kokkotou, E. G., Stavrakis, D. G., Margolis, K. G., Thomou, T., Giorgadze, N., Kirkland, J. L., & Pothoulakis, C. (2011) · Endocrinology · doi:10.1210/en.2011-1170 · Cited by 38
Short-term heat stress altered metabolism and insulin signaling in skeletal muscle
Ganesan, S., Summers, C. M., Pearce, S., Gabler, N. K., Valentine, R. J., Baumgard, L. H., Rhoads, R. P., & Selsby, J. T. (2018) · Journal of Animal Science · doi:10.1093/jas/skx083 · Cited by 37
Oleate dose-dependently regulates palmitate metabolism and insulin signaling in C2C12 myotubes
Capel, F., Cheraïti, N., Acquaviva, C., Hénique, C., Bertrand‐Michel, J., Vianey‐Saban, C., Prip‐Buus, C., & Morio, B. (2016) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2016.10.002 · Cited by 37
Acute Biophysical Responses and Psychological Effects of Different Types of Forests in Patients With Metabolic Syndrome
Lee, K. J., Hur, J., Yang, K., Lee, M.-K., & Lee, S. J. (2017) · Environment and Behavior · doi:10.1177/0013916517700957 · Cited by 36
One-leg inactivity induces a reduction in mitochondrial oxidative capacity, intramyocellular lipid accumulation and reduced insulin signalling upon lipid infusion: a human study with unilateral limb suspension
Bilet, L., Phielix, E., van de Weijer, T., Gemmink, A., Bosma, M., Moonen‐Kornips, E., Jörgensen, J. A., Schaart, G., Zhang, D., Meijer, K., et al. (2020) · Diabetologia · doi:10.1007/s00125-020-05128-1 · Cited by 37
Self-citation
CNTF: a target therapeutic for obesity-related metabolic disease?
Matthews, V. B., & Febbraio, M. A. (2008) · Journal of Molecular Medicine · doi:10.1007/s00109-007-0286-y · Cited by 36
NOD1: An Interface Between Innate Immunity and Insulin Resistance
RIVERS, S. L., Klip, A., & Giacca, A. (2019) · Endocrinology · doi:10.1210/en.2018-01061 · Cited by 36
Insulin Sensitizing and Anti-Inflammatory Effects of Thiazolidinediones Are Heightened in Obese Patients
Esterson, Y. B., Zhang, K., Koppaka, S., Kehlenbrink, S., Kishore, P., Raghavan, P., Maginley, S. R., Carey, M., & Hawkins, M. (2013) · Journal of Investigative Medicine · doi:10.2310/jim.0000000000000017 · Cited by 34
The macrophage at the intersection of immunity and metabolism in obesity
Samaan, M. C. (2011) · Diabetology & Metabolic Syndrome · doi:10.1186/1758-5996-3-29 · Cited by 34
Defining lipid mediators of insulin resistance: controversies and challenges
Metcalfe, L. K., Smith, G. C., & Turner, N. A. (2018) · Journal of Molecular Endocrinology · doi:10.1530/jme-18-0023 · Cited by 35
Exercise reverses high-fat diet-induced impairments on compartmentalization and activation of components of the insulin-signaling cascade in skeletal muscle
Yaspelkis, B. B., Lessard, S. J., Reeder, D. W., Limon, J. J., Saito, M., Rivas, D. A., Kvasha, I. A., & Hawley, J. A. (2007) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00230.2007 · Cited by 34
A Central Role of RLIP76 in Regulation of Glycemic Control
Awasthi, S., Singhal, S. S., Yadav, S., Singhal, J., Vatsyayan, R., Zając, E., Luchowski, R., Borvak, J., Gryczynski, K., & Awasthi, S. (2009) · Diabetes · doi:10.2337/db09-0911 · Cited by 35
Immunometabolic cross-talk in the inflamed heart
Marelli‐Berg, F. M., & Aksentijević, D. (2019) · Cell Stress · doi:10.15698/cst2019.08.194 · Cited by 36
Resveratrol prevents insulin resistance caused by short-term elevation of free fatty acids in vivo
Pereira, S., Park, E., Moore, J., Faubert, B., Breen, D. M., Oprescu, A. I., Nahle, A., Kwan, D., Giacca, A., & Tsiani, E. (2015) · Applied Physiology, Nutrition, and Metabolism · doi:10.1139/apnm-2015-0075 · Cited by 34
Fatty Acids Cause Alterations of Human Arterial Smooth Muscle Cell Proteoglycans That Increase the Affinity for Low-Density Lipoprotein
Rodrı́guez-Lee, M., Östergren‐Lundén, G., Wallin, B., Moses, J., Bondjers, G., & Camejo, G. (2005) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000191659.94059.62 · Cited by 33
AMPK and Beyond: The Signaling Network Controlling RabGAPs and Contraction-Mediated Glucose Uptake in Skeletal Muscle
Peifer‐Weiß, L., Al‐Hasani, H., & Chadt, A. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25031910 · Cited by 39
Fructose and Fructans: Opposite Effects on Health?
Bartolomeo, F. D., & den Ende, W. V. (2015) · Plant Foods for Human Nutrition · doi:10.1007/s11130-015-0485-6 · Cited by 31
Linking obesity with type 2 diabetes: the role of T-bet
Sutherland, A. P. R., Wali, J. A., & Thomas, H. (2014) · Diabetes Metabolic Syndrome and Obesity · doi:10.2147/dmso.s51432 · Cited by 34
Regulation of Lipid Metabolism by Glucocorticoids and 11β-HSD1 in Skeletal Muscle
Morgan, S., Gathercole, L., Simonet, C., Hassan-Smith, Z. K., Bujalska, I. J., Guest, P., Abrahams, L., Smith, D. M., Stewart, P. M., Lavery, G. G., et al. (2013) · Endocrinology · doi:10.1210/en.2012-2214 · Cited by 31
Chronic unpredictable stress regulates visceral adipocyte-mediated glucose metabolism and inflammatory circuits in male rats
Karagiannides, I., Golovatscka, V., Bakirtzi, K., Sideri, A., Salas, M. C., Stavrakis, D. G., Polytarchou, C., Iliopoulos, D., Pothoulakis, C., & Bradesi, S. (2014) · Physiological Reports · doi:10.14814/phy2.284 · Cited by 33
Deletion of interleukin 1 receptor-associated kinase 1 (Irak1) improves glucose tolerance primarily by increasing insulin sensitivity in skeletal muscle
Sun, X., Kim, S. P., Zhang, D., Sun, H. Y., Cao, Q., Lü, X., Ying, Z., Li, L., Henry, R. R., Ciaraldi, T. P., et al. (2017) · Journal of Biological Chemistry · doi:10.1074/jbc.m117.779108 · Cited by 29
Reactive oxygen species production is increased in the peripheral blood monocytes of obese patients
Degasperi, G. R., Denis, R., Morari, J., Solon, C., Geloneze, B., Stabe, C. F. C., Pareja, J. C., Vercesi, A. E., & Velloso, L. A. (2009) · Metabolism · doi:10.1016/j.metabol.2009.04.002 · Cited by 31
Inhibition of malonyl-CoA decarboxylase reduces the inflammatory response associated with insulin resistance
Samokhvalov, V., Ussher, J. R., Fillmore, N., Armstrong, I. K. G., Keung, W., Moroz, D., Lopaschuk, D. G., Seubert, J. M., & Lopaschuk, G. D. (2012) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00018.2012 · Cited by 31
Impact of insulin deprivation and treatment on sphingolipid distribution in different muscle subcellular compartments of streptozotocin-diabetic C57Bl/6 mice
Zabielski, P., Blachnio-Zabielska, A., Lanza, I. R., Gopala, S., Manjunatha, S., Jakaitis, D. R., Persson, X.-M., Gransee, J., Klaus, K. A., Schimke, J. M., et al. (2014) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00610.2012 · Cited by 30
Short-term thermoneutral housing alters glucose metabolism and markers of adipose tissue browning in response to a high-fat diet in lean mice
Clayton, Z. S., & McCurdy, C. E. (2018) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00364.2017 · Cited by 30
Distinct subcellular localisation of intramyocellular lipids and reduced PKCε/PKCθ activity preserve muscle insulin sensitivity in exercise-trained mice
Gaspar, R. C., Lyu, K., Hubbard, B. T., Leitner, B. P., Luukkonen, P. K., Hirabara, S. M., Sakuma, I., Nasiri, A. R., Zhang, D., Kahn, M., et al. (2022) · Diabetologia · doi:10.1007/s00125-022-05838-8 · Cited by 28
Self-citation
The role of glycogen synthase in the development of hyperglycemia in type 2 diabetes – ‘To store or not to store glucose, that's the question’
Beck‐Nielsen, H. (2012) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.2337 · Cited by 30
Mitochondrial Uncoupling Coordinated With PDH Activation Safely Ameliorates Hyperglycemia via Promoting Glucose Oxidation
Jiang, H., Jin, J., Duan, Y., Xie, Z., Li, Y., Gao, A., Gu, M., Zhang, X., Peng, C. S., Xia, C., et al. (2019) · Diabetes · doi:10.2337/db19-0589 · Cited by 29
EDdb: A web resource for eating disorder and its application to identify an extended adipocytokine signaling pathway related to eating disorder
Zhao, M., Li, X., & Qu, H. (2013) · Science China Life Sciences · doi:10.1007/s11427-013-4573-2 · Cited by 29
AdipoRon Alleviates Free Fatty Acid-Induced Myocardial Cell Injury Via Suppressing Nlrp3 Inflammasome Activation
Zhang, Y., Zhang, Y.-L., Huang, Q., Huang, C., Jiang, Z., Cai, F., & Shen, J. (2019) · Diabetes Metabolic Syndrome and Obesity · doi:10.2147/dmso.s221841 · Cited by 28
Glycosphingolipids in Diabetes, Oxidative Stress, and Cardiovascular Disease: Prevention in Experimental Animal Models
Balram, A., Thapa, S., & Chatterjee, S. B. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232315442 · Cited by 30
Knockout of the predominant conventional PKC isoform, PKCα, in mouse skeletal muscle does not affect contraction-stimulated glucose uptake
Jensen, T. E., Maarbjerg, S., Rose, A. J., Leitges, M., & Richter, E. A. (2009) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.90610.2008 · Cited by 29
Protein kinase C isozymes as potential therapeutic targets in immune disorders
Lee, M. R., Duan, W., & Tan, S. (2008) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728222.12.5.535 · Cited by 28
Inflammatory signaling in skeletal muscle insulin resistance: green signal for nutritional intervention?
Hommelberg, P. P. H., LANGEN, R. C. J., Schols, A. M. W. J., Mensink, R. P., & Plat, J. (2010) · Current Opinion in Clinical Nutrition & Metabolic Care · doi:10.1097/mco.0b013e32833f1acd · Cited by 29

Authors: Kim, J. K., Fillmore, J. J., Sunshine, M. J., Albrecht, B., Higashimori, T., Kim, D.-W., Liu, Z.-X., Soos, T. J., Cline, G. W., O’Brien, W. R., Littman, D. R., & Shulman, G. I.
Affiliations: Yale University (US)
Howard Hughes Medical Institute (US)
Corresponding author: Kim, Jason K.
ORCID: Kim, Jason K.
Sunshine, Mary Jean
Kim, Dong-Wook
Cline, Gary W.
Littman, Dan R.
Shulman, Gerald I.
Venue: Journal of Clinical Investigation
Publisher: American Society for Clinical Investigation
Published: 2004-09-15
Volume: 114
Issue: 6
Pages: 823-827
ISSN: 0021-9738 (ISSN-L)
DOI: 10.1172/jci200422230
PMC: PMC516267
OpenAlex: W2119595824
Cited by: 500
References: 31
Citations by year: 2026: 6 · 2025: 6 · 2024: 8 · 2023: 5 · 2022: 13 · 2021: 13 · 2020: 14 · 2019: 18 · 2018: 18 · 2017: 17 · 2016: 16 · 2015: 22 · 2014: 21 · 2013: 35 · 2012: 35
FWCI: 11.49
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Journal of Clinical Investigation (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
YUHSpace (Yonsei University Medical Library) (submittedVersion, cc-by-nc-nd)
Funders: Howard Hughes Medical Institute
American Diabetes Association
Yale University
U.S. Public Health Service (P30 DK45735, R01 DK-40936)
National Institute of Diabetes and Digestive and Kidney Diseases (P30DK45735, R01-DK40936, U24DK59635, R01DK080756, R01DK040936, U24DK059635, P30DK045735)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
Keywords: protein kinase C theta, skeletal muscle insulin signaling, type 2 diabetes, lipid infusion, insulin-stimulated glucose uptake, IRS-1 tyrosine phosphorylation, hyperinsulinemic-euglycemic clamp, hepatic insulin action, therapeutic target
MeSH terms: Protein Kinase C-theta, Adipose Tissue, Animals, Blood Glucose, Diabetes Mellitus, Type 2, Fatty Acids, Nonesterified, Infusions, Intravenous, Insulin, Insulin Resistance, Isoenzymes, Lipids, Phosphoproteins, Phosphorylation, Protein Kinase C, Signal Transduction, Mice, Knockout, Muscle, Skeletal, Mice, Insulin Receptor Substrate Proteins

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

PKC-θ knockout mice are protected from fat-induced insulin resistance

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Citations

Cites

Cited by

Related

Metadata

Record

About these checks