Regulation of Insulin-Stimulated Glucose Transporter GLUT4 Translocation and Akt Kinase Activity by Ceramide
Open accessAbstract
The sphingomyelin derivative ceramide is a signaling molecule implicated in numerous physiological events. Recently published reports indicate that ceramide levels are elevated in insulin-responsive tissues of diabetic animals and that agents which trigger ceramide production inhibit insulin signaling. In the present series of studies, the short-chain ceramide analog C2-ceramide inhibited insulin-stimulated glucose transport by approximately 50% in 3T3-L1 adipocytes, with similar reductions in hormone-stimulated translocation of the insulin-responsive glucose transporter (GLUT4) and insulin-responsive aminopeptidase. C2-ceramide also inhibited phosphorylation and activation of Akt, a molecule proposed to mediate multiple insulin-stimulated metabolic events. C2-ceramide, at concentrations which antagonized activation of both glucose uptake and Akt, had no effect on the tyrosine phosphorylation of insulin receptor substrate 1 (IRS-1) or the amounts of p85 protein and phosphatidylinositol kinase activity that immunoprecipitated with anti-IRS-1 or antiphosphotyrosine antibodies. Moreover, C2-ceramide also inhibited stimulation of Akt by platelet-derived growth factor, an event that is IRS-1 independent. C2-ceramide did not inhibit insulin-stimulated phosphorylation of mitogen-activated protein kinase or pp70 S6-kinase, and it actually stimulated phosphorylation of the latter in the absence of insulin. Various pharmacological agents, including the immunosuppressant rapamycin, the protein synthesis inhibitor cycloheximide, and several protein kinase C inhibitors, were without effect on ceramide's inhibition of Akt. These studies demonstrate ceramide's capacity to inhibit activation of Akt and imply that this is a mechanism of antagonism of insulin-dependent physiological events, such as the peripheral activation of glucose transport and the suppression of apoptosis.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
Ceramides can directly induce cellular IR by blocking the downstream effects of insulin signalling, such as glucose transporter-4 (GLUT4) translocation.
“Ceramides can directly induce cellular IR by blocking the downstream effects of insulin signalling, such as glucose transporter‐4 (GLUT4) translocation.[ 52 ]”
From Pathogenesis of sarcopenia and the relationship with fat mass: descriptive review (2022) · cites this paper as [52]
Ceramide levels were found to be higher in obese and insulin-resistant individuals compared to insulin-sensitive muscle.
“Ceramide levels were found to be higher in obese and insulin‐resistant individuals compared to insulin‐sensitive muscle.”
From Pathogenesis of sarcopenia and the relationship with fat mass: descriptive review (2022) · cites this paper as [52]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Mechanism of activation of protein kinase B by insulin and IGF‐1.
Alessi, D. R., Andjelković, M., Caudwell, B., Cron, P. D., MORRICE, N. A., Cohen, P., & Hemmings, B. A. (1996) · The EMBO Journal · doi:10.1002/j.1460-2075.1996.tb01045.x · Cited by 2,985 · see citing works
Protein kinase B (c-Akt) in phosphatidylinositol-3-OH kinase signal transduction
Burgering, B. M. T., & Coffer, P. J. (1995) · Nature · doi:10.1038/376599a0 · Cited by 2,113 · see citing works
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 · see citing works
PI3K: Downstream AKTion Blocks Apoptosis
Franke, T. F., Kaplan, D. R., & Cantley, L. C. (1997) · Cell · doi:10.1016/s0092-8674(00)81883-8 · Cited by 1,692 · see citing works
Structure of the insulin receptor substrate IRS-1 defines a unique signal transduction protein
Sun, X. J., Rothenberg, P., Kahn, C. R., Backer, J. M., Araki, E., Wilden, P. A., Cahill, D. A., Goldstein, B. J., & White, M. F. (1991) · Nature · doi:10.1038/352073a0 · Cited by 1,574 · see citing works
Tumor Necrosis Factor α: A Key Component of the Obesity-Diabetes Link
Hotamışlıgil, G. S., & Spiegelman, B. M. (1994) · Diabetes · doi:10.2337/diab.43.11.1271 · Cited by 1,344 · see citing works
Kohn, A. D., Summers, S. A., Birnbaum, M. J., & Roth, R. A. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.49.31372 · Cited by 1,284 · see citing works
Self-citationThe sphingomyelin cycle and the second messenger function of ceramide.
Hannun, Y. A. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)41834-5 · Cited by 1,251 · see citing works
Fatty acid-induced β cell apoptosis: A link between obesity and diabetes
Shimabukuro, M., Zhou, Y.-T., Levi, M., & Unger, R. H. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.5.2498 · Cited by 1,142 · see citing works
Cheatham, B., Vlahos, C. J., Cheatham, L. A., Wang, L., Blenis, J., & Kahn, C. R. (1994) · Molecular and Cellular Biology · doi:10.1128/mcb.14.7.4902-4911.1994 · Cited by 1,067 · see citing works
A Retroviral Oncogene, akt , Encoding a Serine-Threonine Kinase Containing an SH2-Like Region
Bellacosa, A., Testa, J. R., Staal, S. P., & Tsichlis, P. N. (1991) · Science · doi:10.1126/science.1833819 · Cited by 939 · see citing works
Okada, T., Kawano, Y., Sakakibara, T., Hazeki, O., & Ui, M. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)41901-6 · Cited by 917 · see citing works
Ceramide: an intracellular signal for apoptosis
Hannun, Y. A. (1995) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(00)88961-6 · Cited by 601 · see citing works
Jones, P. F., Jakubowicz, T., Pitossi, F. J., Maurer, F., & Hemmings, B. A. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.10.4171 · Cited by 532 · see citing works
Andjelkovic, M., Jakubowicz, T., Cron, P., Ming, X., Han, J. W., & Hemmings, B. (1996) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.93.12.5699 · Cited by 525 · see citing works
Coffer, P. J., & Woodgett, J. R. (1991) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1991.tb16305.x · Cited by 493 · see citing works
Peraldi, P., Hotamisligil, G. S., Buurman, W. A., White, M. F., & Spiegelman, B. M. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.22.13018 · Cited by 412 · see citing works
Cong, L.-N., Chen, H., Li, Y., Zhou, L., McGibbon, M. A., Taylor, S. I., & Quon, M. J. (1997) · Molecular Endocrinology · doi:10.1210/mend.11.13.0027 · Cited by 383 · see citing works
Ceramide stimulates a cytosolic protein phosphatase.
Dobrowsky, R., & Hannun, Y. A. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)42727-5 · Cited by 376 · see citing works
A retroviral oncogene, akt, encoding a serine-threonine kinase containing an SH2-like region
Bellacosa, A., Testa, Staal, S., et al. (1991) · Science · doi:10.1126/science.254.5029.274 · Cited by 365 · see citing works
Clarke, J. F., Young, P. W., Yonezawa, K., Kasuga, M., & Holman, G. D. (1994) · Biochemical Journal · doi:10.1042/bj3000631 · Cited by 358 · see citing works
Ueki, K., Yamamoto‐Honda, R., Kaburagi, Y., Yamauchi, T., Tobe, K., Burgering, B. M. T., Coffer, P. J., Komuro, I., Akanuma, Y., Yazaki, Y., et al. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.9.5315 · Cited by 356 · see citing works
Kohn, A. D., Kovacina, K. S., & Roth, R. A. (1995) · The EMBO Journal · doi:10.1002/j.1460-2075.1995.tb00103.x · Cited by 355 · see citing works
Kohn, A. D., Barthel, A., Kovacina, K., Boge, A., Wallach, B., Summers, S., Birnbaum, M., Scott, P. H., Lawrence, J., & Roth, R. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.19.11937 · Cited by 340 · see citing works
Self-citationThe Effects of Wortmannin on Rat Skeletal Muscle
Yeh, J., Gulve, E. A., Rameh, L. E., & Birnbaum, M. J. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.5.2107 · Cited by 313 · see citing works
Self-citation1,2-Diacylglycerol and ceramide levels in insulin-resistant tissues of the rat in vivo.
Turinsky, J., O'Sullivan, D. M., & Bayly, B. P. (1990) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)44844-7 · Cited by 269 · see citing works
Potential Role of Protein Kinase B in Glucose Transporter 4 Translocation in Adipocytes
Tanti, J., Grillo, S., Grémeaux, T., Coffer, P. J., OBBERGHEN, E. V., & MARCHAND‐BRUSTEL, Y. L. (1997) · Endocrinology · doi:10.1210/endo.138.5.5136 · Cited by 261 · see citing works
Martin, S. S., Haruta, T., Morris, A. J., et al. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.30.17605 · Cited by 242 · see citing works
Stress-induced apoptosis and the sphingomyelin pathway
Peña, L. A., Fuks, Z., & Koksnick, R. (1997) · Biochemical Pharmacology · doi:10.1016/s0006-2952(96)00834-9 · Cited by 239 · see citing works
Lipid-Regulated Kinases: Some Common Themes at Last
Downward, J. (1998) · Science · doi:10.1126/science.279.5351.673 · Cited by 198 · see citing works
Early events in TNF signaling: a story of associations and dissociations
Darnay, B. G., & Aggarwal, B. B. (1997) · Journal of Leukocyte Biology · doi:10.1002/jlb.61.5.559 · Cited by 195 · see citing works
Katagiri, H., Asano, T., Ishihara, H., Inukai, K., Shibasaki, Y., Kikuchi, M., Yazaki, Y., & Oka, Y. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.29.16987 · Cited by 194 · see citing works
Frevert, E. U., & Kahn, B. B. (1997) · Molecular and Cellular Biology · doi:10.1128/mcb.17.1.190 · Cited by 178 · see citing works
Kanety, H., Hemi, R., Papa, M. Z., & Karasik, A. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.17.9895 · Cited by 153 · see citing works
Characterization of the Insulin-regulated Membrane Aminopeptidase in 3T3-L1 Adipocytes
Ross, S. A., Scott, H. M., Morris, N. J., Leung, W., Mao, F., Lienhard, G. E., & Keller, S. R. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.6.3328 · Cited by 151 · see citing works
Insulin-stimulated GLUT4 Translocation Is Mediated by a Divergent Intracellular Signaling Pathway
Haruta, T., Morris, A. J., Rose, D. W., Nelson, J. G., Mueckler, M., & Olefsky, J. M. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.47.27991 · Cited by 142 · see citing works
Kotani, K., Carozzi, A., Sakaue, H., Hara, K., Robinson, L. J., Clark, S. F., Yonezawa, K., James, D. E., & Kasuga, M. (1995) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1995.1509 · Cited by 142 · see citing works
Mastick, C. C., Aebersold, R., & Lienhard, G. E. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)37573-7 · Cited by 132 · see citing works
The major protein of GLUT4-containing vesicles, gp160, has aminopeptidase activity.
Kandror, K. V., Li, Y., & Pilch, P. F. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)47348-6 · Cited by 129 · see citing works
Ceramide and the induction of apoptosis.
Jarvis, W. D., Grant, S., & Kolesnick, R. (1996) · PubMed · Cited by 125 · see citing works
Wang, C., O'Brien, L., & Brindley, D. N. (1998) · Diabetes · doi:10.2337/diab.47.1.24 · Cited by 111 · see citing works
Stempka, L., Girod, A., Müller, H., et al. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.10.6805 · Cited by 107 · see citing works
Molecular Cloning of Rat RAC Protein Kinase α and β and Their Association with Protein Kinase Cζ
Konishi, H., Shinomura, T., Kuroda, S., et al. (1994) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1994.2738 · Cited by 71 · see citing works
A role for the serine/threonine kinase, Akt, in insulin-stimulated glucose uptake
Summers, S. A., & Birnbaum, M. J. (1997) · Biochemical Society Transactions · doi:10.1042/bst0250981 · Cited by 68 · see citing works
Self-citationPolyoma Middle T Antigen Activates the Ser/Thr Kinase Akt in a PI3-Kinase-Dependent Manner
Summers, S. A., Lipfert, L., & Birnbaum, M. J. (1998) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1998.8575 · Cited by 56 · see citing works
Self-citationCeramide‐activated protein phosphatase‐2A activity in insulin‐secreting cells
Kowluru, A., & Metz, S. A. (1997) · FEBS Letters · doi:10.1016/s0014-5793(97)01379-3 · Cited by 54 · see citing works
Ceramide‐induced translocation of protein kinase C ζ in primary cultures of astrocytes
Galve‐Roperh, I., Haro, A., & Díaz‐Laviada, I. (1997) · FEBS Letters · doi:10.1016/s0014-5793(97)00985-x · Cited by 40 · see citing works
Cormont, M., Grémeaux, T., Tanti, J., et al. (1992) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1992.tb17036.x · Cited by 13 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Cellular survival: a play in three Akts
Datta, S. R., Brunet, A., & Greenberg, M. E. (1999) · Genes & Development · doi:10.1101/gad.13.22.2905 · Cited by 4,216 · see citing works
Mechanisms of Insulin Action and Insulin Resistance
Petersen, M. C., & Shulman, G. I. (2018) · Physiological Reviews · doi:10.1152/physrev.00063.2017 · Cited by 3,028 · see citing works
Reactive oxygen species have a causal role in multiple forms of insulin resistance
Houstis, N., Rosen, E. D., & Lander, E. S. (2006) · Nature · doi:10.1038/nature04634 · Cited by 2,525 · see citing works
Adipocyte dysfunctions linking obesity to insulin resistance and type 2 diabetes.
Guilherme, A., Virbasius, J. V., Puri, V., & Czech, M. P. (2008) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2391 · Cited by 2,292 · see citing works
Holland, W. L., Brozinick, J. T., Wang, L.-P., Hawkins, E. D., Sargent, K. M., Liu, Y., Narra, K., Hoehn, K. L., Knotts, T. A., Siesky, A., et al. (2007) · Cell Metabolism · doi:10.1016/j.cmet.2007.01.002 · Cited by 1,232 · see citing works
Self-citationAdapting to obesity with adipose tissue inflammation
Reilly, S. M., & Saltiel, A. R. (2017) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2017.90 · Cited by 1,204 · see citing works
Glucolipotoxicity: fuel excess and β-cell dysfunction
Poitout, V., & Robertson, R. P. (2008) · Endocrine Reviews · doi:10.1210/er.2007-0023 · Cited by 1,092 · see citing works
Morino, K., Petersen, K. F., & Shulman, G. I. (2006) · Diabetes · doi:10.2337/db06-s002 · Cited by 853 · see citing works
Reactive oxygen species in health and disease
Alfadda, A. A., & Sallam, R. M. (2012) · Journal of Biomedicine and Biotechnology · doi:10.1155/2012/936486 · Cited by 824 · see citing works
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 · see citing works
Prevention of fat-induced insulin resistance by salicylate
Kim, J. K., Kim, Y.-J., Fillmore, J. J., Chen, Y., Moore, I., Lee, J., Yuan, M., Li, Z. W., Karin, M., Perret, P., et al. (2001) · Journal of Clinical Investigation · doi:10.1172/jci11559 · Cited by 737 · see citing works
Holland, W. L., Bikman, B. T., Wang, L.-P., Yuguang, G., Sargent, K. M., Bulchand, S., Knotts, T. A., Shui, G., Clegg, D. J., Wenk, M. R., et al. (2011) · Journal of Clinical Investigation · doi:10.1172/jci43378 · Cited by 705 · see citing works
Self-citationAMP-activated protein kinase-deficient mice are resistant to the metabolic effects of resveratrol
Um, J.-H., Park, S.-J., Kang, H., Yang, S., Foretz, M., McBurney, M. W., Kim, M. K., Viollet, B., & Chung, J. H. (2010) · Diabetes · doi:10.2337/db09-0482 · Cited by 647 · see citing works
Pathogenesis of sarcopenia and the relationship with fat mass: descriptive review
Li, C., Yu, K., Shyh‐Chang, N., Jiang, Z., Liu, T., Ma, S., Luo, L., Guang, L., Liang, K., Ma, W., et al. (2022) · Journal of Cachexia, Sarcopenia and Muscle · doi:10.1002/jcsm.12901 · Cited by 626 · see citing works
Chavez, J. A., Knotts, T. A., Wang, L.-P., Li, G., Dobrowsky, R. T., Florant, G. L., & Summers, S. A. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m212307200 · Cited by 617 · see citing works
Self-citationSchmitz-Peiffer, C., Craig, D. L., & Biden, T. J. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.34.24202 · Cited by 592 · see citing works
The cell biology of fat expansion
Rutkowski, J. M., Stern, J. H., & Scherer, P. E. (2015) · Journal of Cell Biology · doi:10.1083/jcb.201409063 · Cited by 541 · see citing works
Chavez, J. A., & Summers, S. A. (2003) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2003.08.020 · Cited by 498 · see citing works
Self-citationAMP kinase and malonyl-CoA: targets for therapy of the metabolic syndrome
Ruderman, N., & Prentki, M. (2004) · Nature Reviews Drug Discovery · doi:10.1038/nrd1344 · Cited by 451 · see citing works
PGC-1α regulation by exercise training and its influences on muscle function and insulin sensitivity
Lira, V. A., Benton, C. R., Yan, Z., & Bonen, A. (2010) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00755.2009 · Cited by 412 · see citing works
Regulation of Insulin Action by Ceramide
Stratford, S., Hoehn, K. L., Liu, F., & Summers, S. A. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m406499200 · Cited by 410 · see citing works
Self-citationDose-Response Effect of Elevated Plasma Free Fatty Acid on Insulin Signaling
Belfort, R., Mandarino, L., Kashyap, S., Wirfel, K., Pratipanawatr, T., Berria, R., DeFronzo, R. A., & Cusi, K. (2005) · Diabetes · doi:10.2337/diabetes.54.6.1640 · Cited by 404 · see citing works
Bruce, C. R., Hoy, A. J., Turner, N., Watt, M. J., Allen, T. L., Carpenter, K., Cooney, G. J., Febbraio, M. A., & Kraegen, E. W. (2009) · Diabetes · doi:10.2337/db08-1078 · Cited by 363 · see citing works
Liu, L., Zhang, Y., Chen, N., Shi, X., Tsang, B., & Yu, Y.-H. (2007) · Journal of Clinical Investigation · doi:10.1172/jci30565 · Cited by 356 · see citing works
Skeletal muscle lipid deposition and insulin resistance: effect of dietary fatty acids and exercise
Corcoran, M. P., Lamon-Fava, S., & Fielding, R. A. (2007) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/85.3.662 · Cited by 341 · see citing works
Wang, D. D., Toledo, E., Hruby, A., Rosner, B. A., Willett, W. C., Sun, Q., Razquin, C., Zheng, Y., Ruiz-Canela, M., Guasch-Ferré, M., et al. (2017) · Circulation · doi:10.1161/circulationaha.116.024261 · Cited by 327 · see citing works
Bruce, C. R., Thrush, A. B., Mertz, V. A., Bezaire, V., Chabowski, A., Heigenhauser, G. J. F., & Dyck, D. J. (2006) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00587.2005 · Cited by 328 · see citing works
Diabetes and apoptosis: lipotoxicity
Kusminski, C. M., Shetty, S., Orci, L., Unger, R. H., & Scherer, P. E. (2009) · Apoptosis · doi:10.1007/s10495-009-0352-8 · Cited by 302 · see citing works
POWELL, D. J., TURBAN, S., GRAY, A., HAJDUCH, E., & HUNDAL, H. S. (2004) · Biochemical Journal · doi:10.1042/bj20040139 · Cited by 267 · see citing works
Engin, A. B. (2017) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-48382-5_8 · Cited by 260 · see citing works
Dimopoulos, N., Watson, M., Sakamoto, K., & Hundal, H. S. (2006) · Biochemical Journal · doi:10.1042/bj20060244 · Cited by 247 · see citing works
O’Connor, J. C., McCusker, R. H., Strle, K., Johnson, R. W., Dantzer, R., & Kelley, K. W. (2008) · Cellular Immunology · doi:10.1016/j.cellimm.2007.09.010 · Cited by 238 · see citing works
Muscle Oxidative Capacity Is a Better Predictor of Insulin Sensitivity than Lipid Status
Bruce, C. R., Anderson, M. J., Carey, A. L., Newman, D. G., Bonen, A., Kriketos, A. D., Cooney, G. J., & Hawley, J. A. (2003) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2003-030791 · Cited by 234 · see citing works
Obesity after spinal cord injury
Gater, D. R. (2007) · Physical Medicine and Rehabilitation Clinics of North America · doi:10.1016/j.pmr.2007.03.004 · Cited by 228 · see citing works
Bruce, C. R., & Dyck, D. J. (2004) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00150.2004 · Cited by 178 · see citing works
Sphingolipids and insulin resistance: the five Ws
Summers, S. A. (2010) · Current Opinion in Lipidology · doi:10.1097/mol.0b013e3283373b66 · Cited by 136 · see citing works
Self-citationLipid metabolism in sarcopenia
Al Saedi, A., Debruin, D. A., Hayes, A., & Hamrick, M. (2022) · Bone · doi:10.1016/j.bone.2022.116539 · Cited by 140 · see citing works
Dyck, D. J. (2009) · Applied Physiology, Nutrition, and Metabolism · doi:10.1139/h09-037 · Cited by 136 · see citing works
Hepatic Insulin Resistance Is Not Pathway Selective in Humans With Nonalcoholic Fatty Liver Disease
ter Horst, K. W., Vatner, D. F., Zhang, D., Cline, G. W., Ackermans, M. T., Nederveen, A. J., Verheij, J., Demirkiran, A., van Wagensveld, B. A., Dallinga-Thie, G. M., et al. (2021) · Diabetes Care · doi:10.2337/dc20-1644 · Cited by 88 · see citing works
Sphingolipids: agents provocateurs in the pathogenesis of insulin resistance
Lipina, C., & Hundal, H. S. (2011) · Diabetologia · doi:10.1007/s00125-011-2127-3 · Cited by 83 · see citing works
Devries, M. C., Samjoo, I. A., Hamadeh, M. J., McCready, C., Raha, S., Watt, M. J., Steinberg, G. R., & Tarnopolsky, M. A. (2013) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2013-2044 · Cited by 82 · see citing works
Mitochondrial involvement in skeletal muscle insulin resistance: A case of imbalanced bioenergetics
Affourtit, C. (2016) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2016.07.008 · Cited by 67 · see citing works
Liu, L., Shi, X., Choi, C. S., Shulman, G. I., Klaus, K., Nair, K. S., Schwartz, G. J., Zhang, Y., Goldberg, I. J., & Yu, Y.-H. (2009) · Diabetes · doi:10.2337/db08-1096 · Cited by 66 · see citing works
PPARs and the orchestration of metabolic fuel selection
Sugden, M. C., Zariwala, M. G., & Holness, M. J. (2009) · Pharmacological Research · doi:10.1016/j.phrs.2009.03.014 · Cited by 64 · see citing works
Ceramide dissociates 3′-phosphoinositide production from pleckstrin homology domain translocation
STRATFORD, S., DEWALD, D. B., & SUMMERS, S. A. (2001) · Biochemical Journal · doi:10.1042/bj3540359 · Cited by 161 · see citing works
Self-citation
- Authors
- Summers, S. A., Garza, L. A., Zhou, H., & Birnbaum, M. J.
- Affiliations
- Howard Hughes Medical Institute (US)
- University of Pennsylvania (US)
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 1998-09
- Volume
- 18
- Issue
- 9
- Pages
- 5457-5464
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- PMC
- PMC109130
- OpenAlex
- W2167497319
- Cited by
- 475
- References
- 48
- Citations by year
- 2026: 9 · 2025: 14 · 2024: 15 · 2023: 18 · 2022: 25 · 2021: 15 · 2020: 22 · 2019: 16 · 2018: 15 · 2017: 17 · 2016: 14 · 2015: 18 · 2014: 14 · 2013: 27 · 2012: 16
- FWCI
- 5.68
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular and Cellular Biology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Pennsylvania
- National Institutes of Health (5r01dk039615-03)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK09375, DK 39615, F32DK009375)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sphingolipid Metabolism and Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Keywords
- ceramide, C2-ceramide, insulin signaling, GLUT4 translocation, glucose transport, Akt kinase, insulin resistance, adipocytes, IRS-1, platelet-derived growth factor, apoptosis, sphingolipids
- MeSH terms
- Animals, Biological Transport, Cell Differentiation, Ceramides, Enzyme Inhibitors, Glucose, Insulin, Monosaccharide Transport Proteins, Muscle Proteins, Protein-Tyrosine Kinases, Proto-Oncogene Proteins, Recombinant Proteins, Sphingosine, Transfection, 3T3 Cells, Protein Serine-Threonine Kinases, Adipocytes, Phosphatidylinositol 3-Kinases, Proto-Oncogene Proteins c-akt, Glucose Transporter Type 4, Mice
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
