The DOI matches its Crossref record; 54 of the 56 references it cites were found in a registry or an index.
Etiology of Insulin Resistance
Open accessAbstract
Type 2 diabetes mellitus is a major cause of morbidity and mortality worldwide, and the prevalence is set to increase dramatically over the coming decades. Understanding the metabolic pathways that lead to type 2 diabetes is therefore an important healthcare objective. Novel investigational techniques based on magnetic resonance spectroscopy (MRS) have allowed real-time insight into the molecular defects in patients with type 2 diabetes, revealing that insulin resistance is a product of decreased insulin-stimulated skeletal muscle glycogen synthesis, which can mostly be attributed to decreased insulin-stimulated glucose transport (Glut 4) activity. This defect appears to be a result of intracellular lipid-induced inhibition of insulin-stimulated insulin-receptor substrate (IRS)-1 tyrosine phosphorylation resulting in reduced IRS-1-associated phosphatidyl inositol 3 kinase activity. The hypothesis that insulin resistance is a result of accumulation of intracellular lipid metabolites (e.g., fatty acyl CoAs, diacylglycerol) in skeletal muscle and hepatocytes is supported by observations in patients and mouse models of lipodystrophy. Furthermore, the increase in hepatic insulin sensitivity observed in patients with type 2 diabetes following weight loss is also accompanied by a significant reduction in intrahepatic fat without any changes in circulating adipocytokines (interleukin-6, resistin, leptin). Finally, recent MRS studies in healthy, lean, elderly subjects and lean insulin-resistant offspring of parents with type 2 diabetes have demonstrated that reduced mitochondrial activity may also lead to increased intramyocellular lipid content and insulin resistance in skeletal muscle in these individuals. In summary, in vivo MRS has proved to be an important tool for elucidating the causal chain of events that causes insulin resistance. Understanding the cellular mechanism(s) of insulin resistance in turn offers the prospect of better targeted and more effective therapeutic interventions for treatment and prevention of type 2 diabetes.
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?
In the citing paper
“an increased intramyocellar fat content and fatty acid metabolites have been shown to play a pivotal role in the development of insulin resistance in skeletal muscle [11–15].”
From Pathogenesis of insulin resistance in skeletal muscle (2010) · cites this paper as [13]
In the citing paper
“Dysregulation of fatty acid metabolism plays a pivotal role in the pathogenesis of insulin resistance in skeletal muscle.”
From Pathogenesis of insulin resistance in skeletal muscle (2010) · cites this paper as [13]
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
International Diabetes Federation 2017
Carracher, A. M., Marathe, P. H., & Close, K. L. (2018) · Journal of Diabetes · doi:10.1111/1753-0407.12644 · Cited by 13,379
The metabolic phenotype in obesity: Fat mass, body fat distribution, and adipose tissue function
Goossens, G. H. (2017) · Obesity Facts · doi:10.1159/000471488 · Cited by 8,481
Economic Costs of Diabetes in the U.S. in 2002
American Diabetes Association (2003) · Diabetes Care · doi:10.2337/diacare.26.3.917 · Cited by 4,147
Mechanisms of fatty acid-induced inhibition of glucose uptake.
Boden, G., Chen, X., Ruiz, J., White, J. V., & Rossetti, L. (1994) · Journal of Clinical Investigation · doi:10.1172/jci117252 · Cited by 3,720
Cellular mechanisms of insulin resistance
Shulman, G. I. (2000) · Journal of Clinical Investigation · doi:10.1172/jci10583 · Cited by 2,714
Self-citationBraissant, O., Foufelle, F., Scotto, C., Dauça, M., & Wahli, W. (1996) · Endocrinology · doi:10.1210/endo.137.1.8536636 · Cited by 2,217
Impaired Mitochondrial Activity in the Insulin-Resistant Offspring of Patients with Type 2 Diabetes
Petersen, K. F., Dufour, S., Befroy, D., Garcia, R., & Shulman, G. I. (2004) · New England Journal of Medicine · doi:10.1056/nejmoa031314 · Cited by 2,193
Self-citationMitochondrial dysfunction in the elderly: possible role in insulin resistance
Petersen, K. F., Befroy, D., Dufour, S., Dziura, J., Ariyan, C., Rothman, D. L., DiPietro, L., Cline, G. W., & Shulman, G. I. (2003) · Science · doi:10.1126/science.1082889 · Cited by 2,107
Self-citationMechanism of free fatty acid-induced insulin resistance in humans.
Roden, M., Price, T. B., Perseghin, G., Petersen, K. F., Rothman, D. L., Cline, G. W., & Shulman, G. I. (1996) · Journal of Clinical Investigation · doi:10.1172/jci118742 · Cited by 1,539
Self-citationMechanism of hepatic insulin resistance in non-alcoholic fatty liver disease
Samuel, V. T., Liu, Z.-X., Qu, X., Elder, B. D., Bilz, S., Befroy, D., Romanelli, A. J., & Shulman, G. I. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m313478200 · Cited by 1,322
Self-citation
Research works printed but not linked: 3
- Williamson, 2004, Primary prevention of type 2 diabetes mellitus by lifestyle intervention, Ann Intern Med, 40, 951
- Szczepaniak, 1999, Measurement of intracellular triglyceride stores by 1H spectroscopy, Am J Physiol, 276, E977
- Londos, 1996, Perilipin, Int J Obes Relat Metab Disord, 20, S97
Cited by
Sorted by citations
Items 801–825 of 825
Metabolic health: unleashing the potential of bioactive compounds
Bhattarai, P., Dahal, M., Tiwari, K., & Nirmal, N. P. (2025) · Elsevier eBooks · doi:10.1016/b978-0-443-28862-3.00007-8
Das, A., Pathak, K., Saikia, R., Sahariah, J. J., Gogoi, S., Pathak, M. P., & Barbhuiya, P. A. (2025) · BENTHAM SCIENCE PUBLISHERS eBooks · doi:10.2174/9789815313178125010009
Ünlü, Y., Stinson, E. J., Krakoff, J. A., & Piaggi, P. (2025) · Metabolism · doi:10.1016/j.metabol.2025.156270
Fouad, T. R., Elraouf, A. S. A., Elshenawy, H., Badra, G., Allah, H. A., & Attia, A. (2025) · Egyptian Liver Journal · doi:10.1186/s43066-025-00436-w
“…lowering of HbA1c and fasting glucose levels could reflect an improvement in the control of blood sugar, yet it does not necessarily indicate IR reduction, as some patients could still have elevated IR levels due to high fasting insulin levels; a condition called residual insulin resistance [19].”
Alterations in glucocorticoid homeostasis following sleeve gastrectomyPreprint
Moser, S. O., Moscalu, A., Roberts, C. F., Winter, D. V., Joos, F. L., Gómez, C., Sheu, E. G., & Odermatt, A. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.09.01.673462
Carbohydrate-Insulin Model In Obesity- An Updated Review
Akyakar, B., & Akdevelıoğlu, Y. (2025) · Journal of Gazi University Health Sciences Institute · doi:10.59124/guhes.1595201
Wang, B., Wu, S., Huang, Z., Zhang, W., Sun, H., Zhu, L.-L., Huang, Y., Zhao, A., & Wang, W. (2025) · Journal of Food Science · doi:10.1111/1750-3841.70713
Protein Profiling and Type 2 Diabetes
Sundsten, T. (2008) · KTH Publication Database DiVA (KTH Royal Institute of Technology)
Parikh, H. M., Elgzyri, T., Alibegovic, A., Hiscock, N., Ekström, O., Eriksson, K.-F., Vaag, A., Groop, L. C., Ström, K., & Hansson, O. (2021) · Figshare · doi:10.6084/m9.figshare.14131032
Xie, X., Yan, J., Chen, X., He, L., Wu, J., & Lu, L. (2026) · BMC Pregnancy and Childbirth · doi:10.1186/s12884-026-08738-6
“…resistance continues to worsen to a certain stage, pancreatic β-cells cannot produce enough insulin to compensate for the worsening tissue insulin resistance (i.e., hyperglycemia and significant T2DM or gestational diabetes stage) [24], and the concentration of ANGPTL8 will gradually decrease.”
Ganisetti, D., & Chaudhry, K. (2026) · Cureus · doi:10.7759/cureus.106642
“Prediabetes represents an early abnormal glucose regulation marked by insulin resistance, chronic low-grade inflammation, oxidative stress, and impaired neuromuscular function [5,6].”
The relationship between glycemic intake and insulin resistance in older women
O’Sullivan, T. A. (2008)
Elouafy, Y., Balahbib, A., Fessikh, M. E., Gharby, S., Omari, N. E., Abdulmonem, W. A., Zengin, G., & Bouyahya, A. (2026) · eFood · doi:10.1002/efd2.70162
Joshi, D. M. (2026) · Biomedical Signal Processing and Control · doi:10.1016/j.bspc.2026.110730
Katiyar, S., Ahmad, S., Bhatt, H., Bisen, A. C., Jaiswal, A. K., Ahmad, I., Kushawaha, A. K., Chhikara, N., Baghel, R., Kumar, P., et al. (2026) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2026.110110
Tang, Y., Xu, Y., Yue, Z., Wang, W., Song, W., Wang, H., Liu, L., Wu, J., & Sun, Z. (2026) · iScience · doi:10.1016/j.isci.2026.117400
“14 In the context of accelerating global population aging, validating the TyG index in this specific demographic is imperative to refine risk stratification and optimize primary prevention strategies for the population bearing the highest burden of mortality.”
Liu, Z., & Chen-Ling, S. (2026) · Maturitas · doi:10.1016/j.maturitas.2026.109138
Benevolent Role of Spices in Management of Metabolic Syndrome
Patel, K., Patil, S., Patel, V., Trivedi, R., & Maheshwari, R. (2026) · Journal of Natural Remedies · doi:10.18311/jnr/2026/52732
Diabetes Mellitus: Review of the Common, Rare, and Uncommon (Conceptual and Metaphorical) Types
Pliszka, M., & Szablewski, L. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27219611
Prospects for Induced Pluripotent Stem Cell Therapy for Diabetes
Drummond, R. J., Ross, J. A., & Mee, P. J. (2010) · Stem cell biology and regenerative medicine · doi:10.1007/978-1-60761-860-7_23
“Although the interplay between these two pathogenic pathways is not fully understood, studies have suggested that a degree of mild insulin resistance might occur long before glucose intolerance develops and prior to b cell dysfunction [ 4 ].”
BackgroundEfeito da natação na sensibilidade periferica a insulina em ratos
Martinelli, T. C. D. P. (2009) · doi:10.47749/t/unicamp.2009.470522
Madureira, E. (2025) · Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) · doi:10.34626/p4vf-q470
(1998) · PubMed · Cited by 2,737
Metadata
- Authors
- Petersen, K. F., & Shulman, G. I.
- Affiliations
- Howard Hughes Medical Institute (US)
- Venue
- The American Journal of Medicine
- Publisher
- Elsevier BV
- Published
- 2006-05
- Volume
- 119
- Issue
- 5
- Pages
- S10-S16
- ISSN
- 0002-9343 (ISSN-L)
- PMC
- PMC2995525
- OpenAlex
- W1982488301
- Cited by
- 825
- References
- 56
- Citations by year
- 2026: 19 · 2025: 25 · 2024: 18 · 2023: 26 · 2022: 18 · 2021: 34 · 2020: 31 · 2019: 26 · 2018: 25 · 2017: 27 · 2016: 44 · 2015: 41 · 2014: 55 · 2013: 52 · 2012: 43
- FWCI
- 10.84
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The American Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (R01AG023686)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK040936)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- insulin resistance, type 2 diabetes, IRS-1 tyrosine phosphorylation, PI3K signaling, intracellular lipid accumulation, fatty acyl-CoA, diacylglycerol, lipodystrophy, hepatic insulin sensitivity, weight loss, intrahepatic fat, mitochondrial dysfunction, intramyocellular lipid, magnetic resonance spectroscopy, adipokines
- MeSH terms
- Diabetes Mellitus, Type 2, Humans, Hypoglycemic Agents, Insulin Resistance, Mitochondria, Magnetic Resonance Spectroscopy, Obesity, Phosphoproteins, Weight Loss, Thiazolidinediones, Glucose Transporter Type 4, 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
