The DOI matches its Crossref record; 19 of the 19 references it cites were found in a registry or an index.
Characterization of signal transduction and glucose transport in skeletal muscle from type 2 diabetic patients
Open accessAbstract
We characterized metabolic and mitogenic signaling pathways in isolated skeletal muscle from well-matched type 2 diabetic and control subjects. Time course studies of the insulin receptor, insulin receptor substrate (IRS)-1/2, and phosphatidylinositol (PI) 3-kinase revealed that signal transduction through this pathway was engaged between 4 and 40 min. Insulin-stimulated (0.6-60 nmol/l) tyrosine phosphorylation of the insulin receptor beta-subunit, mitogen-activated protein (MAP) kinase phosphorylation, and glycogen synthase activity were not altered in type 2 diabetic subjects. In contrast, insulin-stimulated tyrosine phosphorylation of IRS-1 and anti-phosphotyrosine-associated PI 3-kinase activity were reduced 40-55% in type 2 diabetic subjects at high insulin concentrations (2.4 and 60 nmol/l, respectively). Impaired glucose transport activity was noted at all insulin concentrations (0.6-60 nmol/l). Aberrant protein expression cannot account for these insulin-signaling defects because expression of insulin receptor, IRS-1, IRS-2, MAP kinase, or glycogen synthase was similar between type 2 diabetic and control subjects. In skeletal muscle from type 2 diabetic subjects, IRS-1 phosphorylation, PI 3-kinase activity, and glucose transport activity were impaired, whereas insulin receptor tyrosine phosphorylation, MAP kinase phosphorylation, and glycogen synthase activity were normal. Impaired insulin signal transduction in skeletal muscle from type 2 diabetic patients may partly account for reduced insulin-stimulated glucose transport; however, additional defects are likely to play a role.
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
“Maintaining the integrity of the IRS-1/PI-3 kinase/Akt pathway is essential for normal insulin-mediated glucose uptake in skeletal muscle ( 26 ).”
From Skeletal Muscle Insulin Resistance Is the Primary Defect in Type 2 Diabetes (2009) · cites this paper as [26]
Experimental — accuracy not yet measuredThe 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 [26]
Experimental — accuracy not yet measuredIn 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 [165]
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 [165]
In the citing paper
“In insulin resistant individuals with T2DM, glucose transport activity is severely impaired [156, 181, 182, 187–189].”
From Pathogenesis of insulin resistance in skeletal muscle (2010) · cites this paper as [189]
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
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
Thomas, J. A., Schlender, K. K., & Larner, J. (1968) · Analytical Biochemistry · doi:10.1016/0003-2697(68)90127-9 · Cited by 1,198
DeFronzo, R. A., Gunnarsson, R., Björkman, O., Olsson, M., & Wahren, J. (1985) · Journal of Clinical Investigation · doi:10.1172/jci111938 · Cited by 1,167
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
Garvey, W. T., Maianu, L., Zhu, J. H., Brechtel-Hook, G., Wallace, P., & Baron, A. D. (1998) · Journal of Clinical Investigation · doi:10.1172/jci1557 · Cited by 459
A microfluorometric method for the determination of free fatty acids in plasma
Miles, J., Glasscock, R., Aikens, J., Gerich, J. E., & Haymond, M. W. (1983) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)38029-9 · Cited by 329
Rothman, D. L., Shulman, R. G., & Shulman, G. I. (1992) · Journal of Clinical Investigation · doi:10.1172/jci115686 · Cited by 327
Vaag, A., Henriksen, J. E., & Beck-Nielsen, H. (1992) · Journal of Clinical Investigation · doi:10.1172/jci115656 · Cited by 299
Dohm, G. L., Tapscott, E. B., Pories, W. J., Dabbs, D. J., Flickinger, E. G., Meelheim, D., Fushiki, T., Atkinson, S., Elton, C. W., & Caro, J. F. (1988) · Journal of Clinical Investigation · doi:10.1172/jci113622 · Cited by 296
Kelley, D. E., Mintun, M. A., Watkins, S. C., Simoneau, J. A., Jadali, F., Fredrickson, A., Beattie, J., & Thériault, R. (1996) · Journal of Clinical Investigation · doi:10.1172/jci118724 · Cited by 228
Roles of Glucose Transport and Glucose Phosphorylation in Muscle Insulin Resistance of NIDDM
Bonadonna, R. C., Bonora, E., Prato, S. D., Saccomani, M. P., Cobelli, C., Natali, A., Frascerra, S., Pecori, N., Ferrannini, E., Bier, D., et al. (1996) · Diabetes · doi:10.2337/diab.45.7.915 · Cited by 191
Arner, P., Pollare, T., Lithell, H., & Livingston, J. N. (1987) · Diabetologia · doi:10.1007/bf00292549 · Cited by 178
Dynamics of Insulin Signaling in 3T3-L1 Adipocytes
Inoue, G., Cheatham, B., Emkey, R., & Kahn, C. R. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.19.11548 · Cited by 166
Thorburn, A. W., Gumbiner, B., Bulacan, F., Brechtel, G., & Henry, R. R. (1991) · Journal of Clinical Investigation · doi:10.1172/jci115022 · Cited by 150
Nolan, J. J. (1994) · Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.78.2.471 · Cited by 108
Andreasson, K., Galuska, D., Thörne, A., SONNENFELD, T., & Wallberg‐Henriksson, H. (1991) · Acta Physiologica Scandinavica · doi:10.1111/j.1748-1716.1991.tb09154.x · Cited by 74
Self-citationZierath, J., Galuska, D., Nolte, L., Thörne, A., Kristensen, J., & Wallberg-Henriksson, H. (1994) · Diabetologia · doi:10.1007/bf00398054 · Cited by 67
Self-citationImpaired Expression of Glycogen Synthase mRNA in Skeletal Muscle of NIDDM Patients
Vestergaard, H., Bjørbæk, C., Andersen, P. H., Bak, J. F., & Pedersen, O. (1991) · Diabetes · doi:10.2337/diab.40.12.1740 · Cited by 64
Klein, H. H., Vestergaard, H., Kotzke, G., & Pedersen, O. (1995) · Diabetes · doi:10.2337/diab.44.11.1310 · Cited by 50
Cited by
Sorted by citations
DeFronzo, R. A. (2009) · Diabetes · doi:10.2337/db09-9028 · Cited by 3,016
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
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
Skeletal 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
“Maintaining the integrity of the IRS-1/PI-3 kinase/Akt pathway is essential for normal insulinmediated glucose uptake in skeletal muscle (26).”
BackgroundPathogenesis 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
Metadata
- Authors
- Krook, A., Björnholm, M., Galuska, D., Jiang, X. J., Fahlman, R., Myers, M. G., Wallberg-Henriksson, H., & Zierath, J. R.
- Affiliations
- Karolinska University Hospital (SE)
- Department of Clinical Physiology, Karolinska Hospital, Stockholm, Sweden.
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2000-02-01
- Volume
- 49
- Issue
- 2
- Pages
- 284-292
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2124948826
- Cited by
- 375
- References
- 19
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 10 · 2023: 5 · 2022: 5 · 2021: 13 · 2020: 7 · 2019: 6 · 2018: 20 · 2017: 11 · 2016: 11 · 2015: 13 · 2014: 15 · 2013: 12 · 2012: 13
- FWCI
- 8.55
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- 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
- type 2 diabetes, skeletal muscle, insulin signaling, insulin receptor, IRS-1, insulin receptor substrate 2, phosphatidylinositol 3-kinase, glucose transport, mitogen-activated protein kinase, glycogen synthase, tyrosine phosphorylation, insulin resistance
- MeSH terms
- Biological Transport, Diabetes Mellitus, Type 2, Glucose, Glycogen Synthase, Humans, Insulin, Male, Middle Aged, Phosphoproteins, Phosphorylation, Receptor, Insulin, Time Factors, Tyrosine, Signal Transduction, Muscle, Skeletal, Phosphotyrosine, 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
