The DOI matches its Crossref record; 47 of the 48 references it cites were found in a registry or an index.
Insulin resistance differentially affects the PI 3-kinase- and MAP kinase-mediated signaling in human muscle
Open accessAbstract
The broad nature of insulin resistant glucose metabolism in skeletal muscle of patients with type 2 diabetes suggests a defect in the proximal part of the insulin signaling network. We sought to identify the pathways compromised in insulin resistance and to test the effect of moderate exercise on whole-body and cellular insulin action. We conducted euglycemic clamps and muscle biopsies on type 2 diabetic patients, obese nondiabetics and lean controls, with and without a single bout of exercise. Insulin stimulation of the phosphatidylinositol 3-kinase (PI 3-kinase) pathway, as measured by phosphorylation of the insulin receptor and IRS-1 and by IRS protein association with p85 and with PI 3-kinase, was dramatically reduced in obese nondiabetics and virtually absent in type 2 diabetic patients. Insulin stimulation of the MAP kinase pathway was normal in obese and diabetic subjects. Insulin stimulation of glucose-disposal correlated with association of p85 with IRS-1. Exercise 24 hours before the euglycemic clamp increased phosphorylation of insulin receptor and IRS-1 in obese and diabetic subjects but did not increase glucose uptake or PI 3-kinase association with IRS-1 upon insulin stimulation. Thus, insulin resistance differentially affects the PI 3-kinase and MAP kinase signaling pathways, and insulin-stimulated IRS-1-association with PI 3-kinase defines a key step in insulin resistance.
Overview
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
Verification
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?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Using the euglycemic insulin clamp with skeletal muscle biopsy, a number of investigators have examined the insulin signal transduction system in human skeletal muscle of type 2 diabetic subjects and consistently demonstrated defects in IRS-1 tyrosine phosphorylation and PI-3 kinase and Akt activation ( 26 , 54 , 55 ).”
From Skeletal Muscle Insulin Resistance Is the Primary Defect in Type 2 Diabetes (2009) · cites this paper as [54]
Experimental — accuracy not yet measuredIn the citing paper
“In contrast, as the MAPK pathway has normal sensitivity to insulin, hyperinsulinemia activates the MAPK pathway, promoting vascular smooth muscle cell growth and activating inflammatory pathways, such as IkB/NF-kB and JNK [107,108].”
From Sarcopenic obesity, insulin resistance, and their implications in cardiovascular and metabolic consequences (2020) · cites this paper as [107]
In the citing paper
“Insulin resistance in skeletal muscle is manifested by decreased insulin-stimulated glucose uptake and results from impaired insulin signaling and multiple post-receptor intracellular defects including impaired glucose transport, glucose phosphorylation, and reduced glucose oxidation and glycogen synthesis.”
From Pathogenesis of insulin resistance in skeletal muscle (2010) · cites this paper as [7]
In the citing paper
“Association of the p85 subunit of PI3K with IRS-1 and activation of PI3K also are greatly attenuated in obese nondiabetic and type 2 diabetic subjects compared with lean healthy controls [7, 165, 166].”
From Pathogenesis of insulin resistance in skeletal muscle (2010) · cites this paper as [7]
In the citing paper
“The ability of insulin to activate insulin receptor and IRS-1 tyrosine phosphorylation in muscle in obese nondiabetic subjects is modestly reduced; whereas in type 2 diabetics insulin-stimulated insulin receptor and IRS-1 tyrosine phosphorylation are severely impaired [7].”
From Pathogenesis of insulin resistance in skeletal muscle (2010) · cites this paper as [7]
In the citing paper
“Most [1, 7, 152, 153, 156, 161] but not all [155] investigators have found a reduction in tyrosine kinase activity that cannot be explained by alterations in insulin receptor number or insulin receptor binding affinity.”
From Pathogenesis of insulin resistance in skeletal muscle (2010) · cites this paper as [7]
In the citing paper
“In insulin-resistant obese nondiabetic subjects, in the NGT insulin resistant offspring of two diabetic parents, and in type 2 diabetic subjects, a substantial decrease in insulin receptor tyrosine phosphorylation has been demonstrated.”
From Pathogenesis of insulin resistance in skeletal muscle (2010) · cites this paper as [7]
In the citing paper
“The decrease in insulin-stimulated association of the p85 regulatory subunit of PI3K with IRS-1 is closely correlated with the reduction in insulin-stimulated muscle glycogen synthase activity and in vivo insulin-stimulated glucose disposal [7].”
From Pathogenesis of insulin resistance in skeletal muscle (2010) · cites this paper as [7]
In the citing paper
“Intact stimulation of the MAPK pathway by insulin in the presence of insulin resistance in the PI3K pathway may play an important role in the development of atherosclerosis [7].”
From Pathogenesis of insulin resistance in skeletal muscle (2010) · cites this paper as [7]
In the citing paper
“Insulin resistance in the PI3K signaling pathway contrasts with an intact stimulation of the MAPK pathway by insulin in insulin-resistant type 2 diabetic and obese nondiabetics individuals [7, 165].”
From Pathogenesis of insulin resistance in skeletal muscle (2010) · cites this paper as [7]
In the citing paper
“Under basal conditions, total glycogen synthase activity in type 2 diabetic subjects is reduced, and the ability of insulin to activate glycogen synthase is severely impaired [7, 215–217].”
From Pathogenesis of insulin resistance in skeletal muscle (2010) · cites this paper as [7]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
PROTEIN MEASUREMENT WITH THE FOLIN PHENOL REAGENT
Lowry, O. H., Rosebrough, N., Farr, A. L., & Randall, R. (1951) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)52451-6 · Cited by 316,394
Alternative pathway of insulin signalling in mice with targeted disruption of the IRS-1 gene
Araki, E., Lipes, M. A., Patti, M.-E., Brüning, J. C., Haag III, B., Johnson, R. S., & Kahn, C. R. (1994) · Nature · doi:10.1038/372186a0 · Cited by 1,252
Self-citationCheatham, 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 1,062
Self-citationMeasurement of Size and Turnover Rate of Body Glucose Pool by the Isotope Dilution Method
Steele, R., Wall, J. S., de Bodo, R. C., & Altszuler, N. (1956) · American Journal of Physiology-Legacy Content · doi:10.1152/ajplegacy.1956.187.1.15 · Cited by 816
Perseghin, G., Price, T. B., Petersen, K. F., Roden, M., Cline, G. W., Gerow, K., Rothman, D. L., & Shulman, G. I. (1996) · New England Journal of Medicine · doi:10.1056/nejm199610313351804 · Cited by 699
Jiang, Z. Y., Lin, Y.-W., Clemont, A., Feener, E. P., Hein, K. D., Igarashi, M., Yamauchi, T., White, M. F., & King, G. L. (1999) · Journal of Clinical Investigation · doi:10.1172/jci5971 · Cited by 604
Dunaif, A., Xia, J., Book, C. B., Schenker, E., & Tang, Z. (1995) · Journal of Clinical Investigation · doi:10.1172/jci118126 · Cited by 561
Effect of physical exercise on sensitivity and responsiveness to insulin in humans
Mikines, K. J., Sonne, B., Farrell, P. A., Tronier, B., & Galbo, H. (1988) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1988.254.3.e248 · Cited by 538
Goodyear, L. J., Giorgino, F., Sherman, L., Carey, J., Smith, R. J., & Dohm, G. L. (1995) · Journal of Clinical Investigation · doi:10.1172/jci117909 · Cited by 527
Ren, J., Semenkovich, C. F., Gulve, E. A., Gao, J. H., & Holloszy, J. O. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)36636-x · Cited by 416
Flagged first, then by citations
1 of the 48 references couldn’t be matched to a known paper.
Research works printed but not linked: 9
- Cheatham, 1994, Mol Cell Biol, 14, 4902, 10.1128/MCB.14.7.4902 · DOI
- Nyomba, 1990, Am J Physiol, 258, E964
- Hayashi, 1997, Am J Physiol, 273, E1039
- Koval, 1998, Am J Physiol, 274, E304
- O’Doherty, 1994, Am J Physiol, 266, E171
- Mikines, 1988, Am J Physiol, 254, E248
- Goodyear, 1995, Am J Physiol, 268, E987
- Zorzano, 1986, Am J Physiol, 251, E664
- Kochan, 1979, Am J Physiol, 236, E660
Cited by
Sorted by citations
Insulin signalling and the regulation of glucose and lipid metabolism
Saltiel, A. R., & Kahn, C. R. (2001) · Nature · doi:10.1038/414799a · Cited by 5,326
Self-citationDeFronzo, R. A. (2009) · Diabetes · doi:10.2337/db09-9028 · Cited by 3,016
Self-citationMechanisms 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
DeFronzo, R. A., Ferrannini, E., Groop, L., Henry, R. R., Herman, W. H., Holst, J. J., Hu, F. B., Kahn, C. R., Raz, I., Shulman, G. I., et al. (2015) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2015.19 · Cited by 2,611
Self-citationSkeletal Muscle Insulin Resistance Is the Primary Defect in Type 2 Diabetes
DeFronzo, R. A., & Tripathy, D. (2009) · Diabetes Care · doi:10.2337/dc09-s302 · Cited by 2,102
“Molecular etiology of the skeletal muscle insulin resistance in genetically predisposed individuals Using the euglycemic insulin clamp with skeletal muscle biopsy, a number of investigators have examined the insulin signal transduction system in human skeletal muscle of type 2 diabetic subjects and consistently demons…”
BackgroundSelf-citationCornier, M.-A., Dabelea, D., Hernandez, T. L., Lindstrom, R. C., Steig, A. J., Stob, N. R., Van Pelt, R. E., Wang, H., & Eckel, R. H. (2008) · Endocrine Reviews · doi:10.1210/er.2008-0024 · Cited by 2,162
Diamanti-Kandarakis, E., & Dunaif, A. (2012) · Endocrine Reviews · doi:10.1210/er.2011-1034 · Cited by 1,947
Patti, M. E., Butte, A. J., Crunkhorn, S., Cusi, K., Berria, R., Kashyap, S., Miyazaki, Y., Kohane, I., Costello, M., Saccone, R., et al. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1032913100 · Cited by 1,952
Self-citationMechanisms, Pathophysiology, and Therapy of Arterial Stiffness
Zieman, S. J., Melenovsky, V., & Kass, D. A. (2005) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/01.atv.0000160548.78317.29 · Cited by 1,854
Kim, J.-A., Montagnani, M., Koh, K. K., & Quon, M. J. (2006) · Circulation · doi:10.1161/circulationaha.105.563213 · Cited by 1,652
Pathogenesis of type 2 diabetes mellitus
DeFronzo, R. A. (2004) · Medical Clinics of North America · doi:10.1016/j.mcna.2004.04.013 · Cited by 1,342
Self-citationGrundy, S. M. (2010) · Springer eBooks · doi:10.1007/978-1-4419-5839-6_1 · Cited by 1,227
Monocyte chemoattractant protein 1 in obesity and insulin resistance
Sartipy, P., & Loskutoff, D. J. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1133870100 · Cited by 1,229
Clinical Update: Cardiovascular Disease in Diabetes Mellitus
Wang, C. C. L., Hess, C. N., Hiatt, W. R., & Goldfine, A. B. (2016) · Circulation · doi:10.1161/circulationaha.116.022194 · Cited by 1,222
Role of Mitochondrial Dysfunction in Insulin Resistance
Kim, J.-A., Wei, Y., & Sowers, J. R. (2008) · Circulation Research · doi:10.1161/circresaha.107.165472 · Cited by 1,103
Copps, K. D., & White, M. F. (2012) · Diabetologia · doi:10.1007/s00125-012-2644-8 · Cited by 1,017
“In contrast with AKT, basal or insulin-stimulated ERK1/2 activation in diabetic muscle is unchanged or increased in several studies, compatible with its partial independence from IR/IRS [82, 86].”
BackgroundResultInfluentialActivation of Protein Kinase C Isoforms and Its Impact on Diabetic Complications
Geraldes, P., & King, G. L. (2010) · Circulation Research · doi:10.1161/circresaha.110.217117 · Cited by 1,019
Type 2 diabetes and cardiovascular disease: Have all risk factors the same strength?
Timon, I. M. (2014) · World Journal of Diabetes · doi:10.4239/wjd.v5.i4.444 · Cited by 1,019
Signaling pathways in insulin action: molecular targets of insulin resistance
Pessin, J. E., & Saltiel, A. R. (2000) · Journal of Clinical Investigation · doi:10.1172/jci10582 · Cited by 939
Cusi, K. J. (2012) · Gastroenterology · doi:10.1053/j.gastro.2012.02.003 · Cited by 940
Self-citationDeFronzo, R. A. (2010) · Diabetologia · doi:10.1007/s00125-010-1684-1 · Cited by 908
Self-citationCardiovascular Actions of Insulin
Muniyappa, R., Montagnani, M., Koh, K. K., & Quon, M. J. (2007) · Endocrine Reviews · doi:10.1210/er.2007-0006 · Cited by 888
FROM MICE TO MEN: Insights into the Insulin Resistance Syndromes
Biddinger, S. B., & Kahn, C. R. (2005) · Annual Review of Physiology · doi:10.1146/annurev.physiol.68.040104.124723 · Cited by 714
Self-citationNew Perspectives into the Molecular Pathogenesis and Treatment of Type 2 Diabetes
Saltiel, A. R. (2001) · Cell · doi:10.1016/s0092-8674(01)00239-2 · Cited by 688
Pathogenesis of insulin resistance in skeletal muscle
Abdul-Ghani, M. A., & DeFronzo, R. A. (2010) · Journal of Biomedicine and Biotechnology · doi:10.1155/2010/476279 · Cited by 670
Self-citationPara-Inflammation in the Aging Retina
Xu, H., Chen, M., & Forrester, J. V. (2009) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2009.06.001 · Cited by 659
Ceramide Content Is Increased in Skeletal Muscle From Obese Insulin-Resistant Humans
Adams, J. M., Pratipanawatr, T., Berria, R., Wang, E. L., DeFronzo, R. A., Sullards, M. C., & Mandarino, L. J. (2004) · Diabetes · doi:10.2337/diabetes.53.1.25 · Cited by 677
Self-citationObesity and polycystic ovary syndrome
Barber, T., McCarthy, M. I., Wass, J. A. H., & Franks, S. (2006) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2006.02587.x · Cited by 655
Insulin resistance and sarcopenia: mechanistic links between common co-morbidities
Cleasby, M. E., Jamieson, P. M., & Atherton, P. J. (2016) · Journal of Endocrinology · doi:10.1530/joe-15-0533 · Cited by 596
Insulin Resistance and Atherosclerosis: Implications for Insulin-Sensitizing Agents
Di Pino, A., & DeFronzo, R. A. (2019) · Endocrine Reviews · doi:10.1210/er.2018-00141 · Cited by 535
Self-citationStefan, N., Vozarova, B., Funahashi, T., Matsuzawa, Y., Weyer, C., Lindsay, R. S., YOUNGREN, J. F., Havel, P. J., Pratley, R. E., Bogardus, C., et al. (2002) · Diabetes · doi:10.2337/diabetes.51.6.1884 · Cited by 557
How does blood glucose control with insulin save lives in intensive care?
den Berghe, G. V. (2004) · Journal of Clinical Investigation · doi:10.1172/jci23506 · Cited by 558
Invited Review: Effects of acute exercise and exercise training on insulin resistance
Henriksen, E. J. (2002) · Journal of Applied Physiology · doi:10.1152/japplphysiol.01219.2001 · Cited by 535
Insulin Resistance, Obesity and Lipotoxicity
Yazıcı, D., & Sezer, H. (2017) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-48382-5_12 · Cited by 525
Taylor, R. (2013) · Diabetes Care · doi:10.2337/dc12-1805 · Cited by 485
Mechanisms of Disease: endothelial dysfunction in insulin resistance and diabetes
Rask‐Madsen, C., & King, G. L. (2006) · Nature Clinical Practice Endocrinology & Metabolism · doi:10.1038/ncpendmet0366 · Cited by 490
Metabolic syndrome: Definition, pathophysiology, and mechanisms
Miranda, P. J., DeFronzo, R. A., Califf, R. M., & Guyton, J. R. (2005) · American Heart Journal · doi:10.1016/j.ahj.2004.07.013 · Cited by 486
Self-citationBiddinger, S. B., Hernandez-Ono, A., Rask-Madsen, C., Haas, J. T., Alemán, J. O., Suzuki, R., Scapa, E. F., Agarwal, C., Carey, M. C., Stephanopoulos, G., et al. (2008) · Cell Metabolism · doi:10.1016/j.cmet.2007.11.013 · Cited by 469
Self-citationIntensive insulin therapy protects the endothelium of critically ill patients
Langouche, L. (2005) · Journal of Clinical Investigation · doi:10.1172/jci25385 · Cited by 467
Volpi, E., Mittendorfer, B., Rasmussen, B. B., & Wolfe, R. R. (2000) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.85.12.7021 · Cited by 464
Lomonaco, R., Ortiz‐Lopez, C., Orsak, B., Webb, A., Hardies, J., Darland, C., Finch, J., Gastaldelli, A., Harrison, S. A., Tio, F. O., et al. (2011) · Hepatology · doi:10.1002/hep.25539 · Cited by 460
Self-citationFrank, N., Geor, R. J., Bailey, S. R., Durham, A. E., & Johnson, P. J. (2010) · Journal of Veterinary Internal Medicine · doi:10.1111/j.1939-1676.2010.0503.x · Cited by 449
Signaling pathways in obesity: mechanisms and therapeutic interventions
Wen, X., Zhang, B., Wu, B., Xiao, H., Li, Z., Li, R., Xu, X., & Li, T. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01149-x · Cited by 490
Endothelial Dysfunction in Obesity and Insulin Resistance: A Road to Diabetes and Heart Disease
Caballero, A. E. (2003) · Obesity Research · doi:10.1038/oby.2003.174 · Cited by 416
Obesity and Polycystic Ovary Syndrome: Implications for Pathogenesis and Novel Management Strategies
Barber, T. M., Hanson, P., Weickert, M. O., & Franks, S. (2019) · Clinical Medicine Insights: Reproductive Health · doi:10.1177/1179558119874042 · Cited by 411
Energy metabolism in health and diseases
Liu, H., Wang, S., Wang, J., Guo, X., Song, Y., Fu, K., Gao, Z., Liu, D., He, W., & Yang, L. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02141-x · Cited by 484
Dose-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
Self-citationObesity and polycystic ovary syndrome
Barber, T. M., & Franks, S. (2021) · Clinical Endocrinology · doi:10.1111/cen.14421 · Cited by 385
Hong, S.-H., & Choi, K. M. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21020494 · Cited by 390
Draznin, B. (2006) · Diabetes · doi:10.2337/db06-0391 · Cited by 404
Elevated Toll-Like Receptor 4 Expression and Signaling in Muscle From Insulin-Resistant Subjects
Reyna, S. M., Ghosh, S., Tantiwong, P., Meka, C. S. R., Eagan, P. A., Jenkinson, C. P., Cersósimo, E., DeFronzo, R. A., Coletta, D. K., Sriwijitkamol, A., et al. (2008) · Diabetes · doi:10.2337/db08-0038 · Cited by 390
Self-citationTargeting hepatic glucose metabolism in the treatment of type 2 diabetes
Rines, A. K., Sharabi, K., Tavares, C. D. J., & Puigserver, P. (2016) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2016.151 · Cited by 390
Federici, M., Menghini, R., Mauriello, A., Hribal, M. L., Ferrelli, F., Lauro, D., Sbraccia, P., Spagnoli, L. G., Sesti, G., & Lauro, R. (2002) · Circulation · doi:10.1161/01.cir.0000023043.02648.51 · Cited by 375
The many actions of insulin in skeletal muscle, the paramount tissue determining glycemia
Sylow, L., Tokarz, V. L., Richter, E. A., & Klip, A. (2021) · Cell Metabolism · doi:10.1016/j.cmet.2021.03.020 · Cited by 366
Bajaj, M. S., Suraamornkul, S., Piper, P. K., Hardies, L. J., Glass, L. C., Cersósimo, E., Pratipanawatr, T., Miyazaki, Y., & DeFronzo, R. A. (2004) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2003-031315 · Cited by 355
Self-citationKim, B., & Feldman, E. L. (2015) · Experimental & Molecular Medicine · doi:10.1038/emm.2015.3 · Cited by 372
eNOS, metabolic syndrome and cardiovascular disease
Huang, P. L. (2009) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2009.03.005 · Cited by 365
Exercise as a therapeutic intervention for the prevention and treatment of insulin resistance
Hawley, J. A. (2004) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.505 · Cited by 344
Parpal, S., Karlsson, M., Thorn, H., & Strålfors, P. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m007454200 · Cited by 339
Defects in insulin receptor signaling in vivo in the polycystic ovary syndrome (PCOS)
Dunaif, A., Wu, X., Lee, A., & Diamanti-Kandarakis, E. (2001) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.2001.281.2.e392 · Cited by 337
Insulin: The master regulator of glucose metabolism
Norton, L., Shannon, C. E., Gastaldelli, A., & DeFronzo, R. A. (2022) · Metabolism · doi:10.1016/j.metabol.2022.155142 · Cited by 367
Self-citationTamura, Y., Tanaka, Y., Sato, F., Choi, J. B., Watada, H., Niwa, M., Kinoshita, J., Ooka, A., Kumashiro, N., Igarashi, Y., et al. (2005) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2004-1959 · Cited by 334
Montagnani, M., Golovchenko, I., Kim, I., Koh, G. Y., Goalstone, M. L., Mundhekar, A. N., Johansen, M. L., Kucik, D. F., Quon, M. J., & Draznin, B. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m103728200 · Cited by 332
Chemistry and Biochemistry of Type 2 Diabetes
Ross, S. A., Gulve, E. A., & Wang, M. (2004) · Chemical Reviews · doi:10.1021/cr0204653 · Cited by 326
Endothelial Dysfunction: Is There a Hyperglycemia-Induced Imbalance of NOX and NOS?
Meza, C. A., La Favor, J. D., Kim, D.-H., & Hickner, R. C. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20153775 · Cited by 323
Insulin resistance in the nervous system
Kim, B., & Feldman, E. L. (2012) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2011.12.004 · Cited by 321
Renin-angiotensin-aldosterone system and oxidative stress in cardiovascular insulin resistance
Cooper, S. A., Whaley-Connell, A., Habibi, J., Wei, Y., Lastra, G., Manrique, C., Stas, S., & Sowers, J. R. (2007) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00522.2007 · Cited by 317
Insulin Resistance and Atherosclerosis
Nigro, J., Osman, N., Dart, A. M., & Little, P. J. (2006) · Endocrine Reviews · doi:10.1210/er.2005-0007 · Cited by 321
Pathophysiologic Approach to Therapy in Patients With Newly Diagnosed Type 2 Diabetes
DeFronzo, R. A., Eldor, R., & Abdul‐Ghani, M. A. (2013) · Diabetes Care · doi:10.2337/dcs13-2011 · Cited by 323
Self-citationBouzakri, K., Roques, M., Gual, P., Espinosa, S., Guebre-Egziabher, F., Riou, J.-P., Laville, M., Le Marchand-Brustel, Y., Tanti, J.-F., & Vidal, H. (2003) · Diabetes · doi:10.2337/diabetes.52.6.1319 · Cited by 305
Pathophysiological implications of insulin resistance on vascular endothelial function
Wheatcroft, S. B., Williams, I. L., Shah, A. M., & Kearney, M. T. (2003) · Diabetic Medicine · doi:10.1046/j.1464-5491.2003.00869.x · Cited by 316
Selective Insulin and Leptin Resistance in Metabolic Disorders
Könner, A. C., & Brüning, J. C. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.07.004 · Cited by 320
Karlsson, H., Zierath, J. R., Kane, S., Krook, A., Lienhard, G. E., & Wallberg‐Henriksson, H. (2005) · Diabetes · doi:10.2337/diabetes.54.6.1692 · Cited by 299
Qin, B., Nagasaki, M., Ren, M., Bajotto, G., Oshida, Y., & Sato, Y. (2003) · Diabetes Research and Clinical Practice · doi:10.1016/s0168-8227(03)00173-6 · Cited by 298
The Role of Adipose Tissue and Lipotoxicity in the Pathogenesis of Type 2 Diabetes
Cusi, K. J. (2010) · Current Diabetes Reports · doi:10.1007/s11892-010-0122-6 · Cited by 311
Self-citationAberrant insulin signaling in Alzheimer's disease: current knowledge
Bedse, G., Domenico, F. D., Serviddio, G., & Cassano, T. (2015) · Frontiers in Neuroscience · doi:10.3389/fnins.2015.00204 · Cited by 313
Skeletal muscle insulin resistance: role of mitochondria and other ROS sources
Di Meo, S., Iossa, S., & Venditti, P. (2017) · Journal of Endocrinology · doi:10.1530/joe-16-0598 · Cited by 282
Adipokines: a link between obesity and dementia?
Kiliaan, A. J., Arnoldussen, I. A. C., & Gustafson, D. (2014) · The Lancet Neurology · doi:10.1016/s1474-4422(14)70085-7 · Cited by 290
Pirola, L., Johnston, A., & OBBERGHEN, E. V. (2004) · Diabetologia · doi:10.1007/s00125-003-1313-3 · Cited by 286
Corbould, A., Kim, Y.-B., Youngren, J. F., Pender, C., Kahn, B. B., Lee, A., & Dunaif, A. (2005) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00361.2004 · Cited by 283
Role of endothelial dysfunction in insulin resistance
Hsueh, W. A., & Quiñones, M. J. (2003) · The American Journal of Cardiology · doi:10.1016/s0002-9149(03)00611-8 · Cited by 271
Role of immune cells in obesity induced low grade inflammation and insulin resistance
Asghar, A., & Sheikh, N. (2017) · Cellular Immunology · doi:10.1016/j.cellimm.2017.03.001 · Cited by 278
Januś, A., Szahidewicz-Krupska, E., Mazur, G. J., & Doroszko, A. (2016) · Mediators of Inflammation · doi:10.1155/2016/3634948 · Cited by 277
Angiotensin II–Induced Insulin Resistance Is Associated With Enhanced Insulin Signaling
Ogihara, T., Asano, T., Ando, K., Chiba, Y., Sakoda, H., Anai, M., Shojima, N., Ono, H., Onishi, Y., Fujishiro, M., et al. (2002) · Hypertension · doi:10.1161/01.hyp.0000040262.48405.a8 · Cited by 275
Belfiore, A., & Malaguarnera, R. (2011) · Endocrine Related Cancer · doi:10.1530/erc-11-0074 · Cited by 272
Cusi, K. J., Chang, Z., Harrison, S., Lomonaco, R., Bril, F., Orsak, B., Ortiz‐Lopez, C., Hecht, J., Feldstein, A. E., Webb, A., et al. (2013) · Journal of Hepatology · doi:10.1016/j.jhep.2013.07.042 · Cited by 272
Self-citationComplementary roles of IRS-1 and IRS-2 in the hepatic regulation of metabolism
Taniguchi, C. M., Ueki, K., & Kahn, C. R. (2005) · Journal of Clinical Investigation · doi:10.1172/jci23187 · Cited by 286
Self-citationRetractedÖst, A., Svensson, K., Ruishalme, I., Brännmark, C., Franck, N., Krook, H., Sandström, P., Kjølhede, P., & Strålfors, P. (2010) · Molecular Medicine · doi:10.2119/molmed.2010.00023 · Cited by 274
Molecular Mechanisms of Insulin Resistance That Impact Cardiovascular Biology
Wang, C. C. L., Goalstone, M. L., & Draznin, B. (2004) · Diabetes · doi:10.2337/diabetes.53.11.2735 · Cited by 274
Signalling aspects of insulin resistance in skeletal muscle
Schmitz‐Peiffer, C. (2000) · Cellular Signalling · doi:10.1016/s0898-6568(00)00110-8 · Cited by 269
The endothelium and vascular inflammation in diabetes
Hartge, M., Unger, T., & Kintscher, U. (2007) · Diabetes and Vascular Disease Research · doi:10.3132/dvdr.2007.025 · Cited by 269
Role of Insulin Resistance and Lipotoxicity in Non-Alcoholic Steatohepatitis
Cusi, K. J. (2009) · Clinics in Liver Disease · doi:10.1016/j.cld.2009.07.009 · Cited by 270
Self-citationRole of c-Jun N-terminal Kinase (JNK) in Obesity and Type 2 Diabetes
Yung, J. H. M., & Giacca, A. (2020) · Cells · doi:10.3390/cells9030706 · Cited by 284
Regulation by Insulin of Gene Expression in Human Skeletal Muscle and Adipose Tissue
Ducluzeau, P., Peretti, N., Laville, M., Andréelli, F., Véga, N., Riou, J. P., & Vidal, H. (2001) · Diabetes · doi:10.2337/diabetes.50.5.1134 · Cited by 263
S-Nitrosylation-dependent Inactivation of Akt/Protein Kinase B in Insulin Resistance
Yasukawa, T., Tokunaga, E., Ota, H., Sugita, H., Martyn, J. A. J., & Kaneki, M. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m411871200 · Cited by 265
Scazzocchio, B., Varı́, R., Filesi, C., D’Archivio, M., Santangelo, C., Giovannini, C., Iacovelli, A., Silecchia, G., Volti, G. L., Galvano, F., et al. (2011) · Diabetes · doi:10.2337/db10-1461 · Cited by 269
Richardson, D. K., Kashyap, S., Bajaj, M., Cusi, K., Mandarino, S. J., Finlayson, J., DeFronzo, R. A., Jenkinson, C. P., & Mandarino, L. J. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m408985200 · Cited by 259
Self-citationGene Expression Profile in Skeletal Muscle of Type 2 Diabetes and the Effect of Insulin Treatment
Sreekumar, R., Halvatsiotis, P., Schimke, J. C., & Nair, K. S. (2002) · Diabetes · doi:10.2337/diabetes.51.6.1913 · Cited by 257
Eckel, R. H., Barouch, W. W., & Ershow, A. G. (2002) · Circulation · doi:10.1161/01.cir.0000017823.53114.4c · Cited by 257
Hwang, H., Bowen, B. P., Lefort, N., Flynn, C. R., De Filippis, E. A., Roberts, C., Smoke, C. C., Meyer, C., Højlund, K., Yi, Z., et al. (2010) · Diabetes · doi:10.2337/db09-0214 · Cited by 255
Self-citation
Metadata
- Authors
- Cusi, K., Maezono, K., Osman, A., Pendergrass, M., Patti, M. E., Pratipanawatr, T., DeFronzo, R. A., Kahn, C. R., & Mandarino, L. J.
- Affiliations
- The University of Texas at San Antonio Health Science Center (US)
- Harvard University (US)
- Tulane University (US)
- Joslin Diabetes Center (US)
- Corresponding author
- Mandarino, Lawrence J.
- ORCID
- Venue
- Journal of Clinical Investigation
- Published
- 2000-02-01
- Volume
- 105
- Issue
- 3
- Pages
- 311-320
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC377440
- OpenAlex
- W2120852510
- Cited by
- 1,139
- References
- 48
- Citations by year
- 2026: 12 · 2025: 13 · 2024: 19 · 2023: 27 · 2022: 35 · 2021: 45 · 2020: 33 · 2019: 35 · 2018: 24 · 2017: 37 · 2016: 52 · 2015: 54 · 2014: 53 · 2013: 57 · 2012: 65
- FWCI
- 13.25
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Diabetes Association
- National Institutes of Health (5k08dk002526-03)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01-DK-24092, DK02526, R01DK047936, R01DK033201, R01DK024092, R01-DK-47936)
- National Center for Research Resources (M01RR001346)
- 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
- insulin resistance, skeletal muscle, type 2 diabetes, PI3K signaling, MAPK signaling, insulin receptor, IRS-1, p85 regulatory subunit, physical activity, glucose uptake, obesity, euglycemic clamp, insulin signaling
- MeSH terms
- Adult, Diabetes Mellitus, Type 2, Female, Humans, Insulin Resistance, Male, Phosphoproteins, Receptor, Insulin, Signal Transduction, Muscle, Skeletal, Phosphatidylinositol 3-Kinases, Mitogen-Activated Protein Kinases, 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
