The DOI matches its Crossref record; 10 of the 10 references it cites were found in a registry or an index.
Sodium Phenylbutyrate, a Drug With Known Capacity to Reduce Endoplasmic Reticulum Stress, Partially Alleviates Lipid-Induced Insulin Resistance and β-Cell Dysfunction in Humans
Open accessAbstract
OBJECTIVE: Chronically elevated free fatty acids contribute to insulin resistance and pancreatic β-cell failure. Among numerous potential factors, the involvement of endoplasmic reticulum (ER) stress has been postulated to play a mechanistic role. Here we examined the efficacy of the chemical chaperone, sodium phenylbutyrate (PBA), a drug with known capacity to reduce ER stress in animal models and in vitro, on lipid-induced insulin resistance and β-cell dysfunction in humans. RESEARCH DESIGN AND METHODS: Eight overweight or obese nondiabetic men underwent four studies each, in random order, 4 to 6 weeks apart. Two studies were preceded by 2 weeks of oral PBA (7.5 g/day), followed by a 48-h i.v. infusion of intralipid/heparin or saline, and two studies were preceded by placebo treatment, followed by similar infusions. Insulin secretion rates (ISRs) and sensitivity (SI) were assessed after the 48-h infusions by hyperglycemic and hyperinsulinemic-euglycemic clamps, respectively. RESULTS: Lipid infusion reduced SI, which was significantly ameliorated by pretreatment with PBA. Absolute ISR was not affected by any treatment; however, PBA partially ameliorated the lipid-induced reduction in the disposition index (DI = ISR × SI), indicating that PBA prevented lipid-induced β-cell dysfunction. CONCLUSIONS: These results suggest that PBA may provide benefits in humans by ameliorating the insulin resistance and β-cell dysfunction induced by prolonged elevation of free fatty acids.
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.
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
Mechanisms linking obesity to insulin resistance and type 2 diabetes
Kahn, S. E., Hull, R. L., & Utzschneider, K. M. (2006) · Nature · doi:10.1038/nature05482 · Cited by 5,448
Yuan, M., Konstantopoulos, N., Lee, J., Hansen, L., Li, Z.-W., Karin, M., & Shoelson, S. E. (2001) · Science · doi:10.1126/science.1061620 · Cited by 1,884
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 · cited 1×
“Several hypotheses have been proposed, including tissue accumulation of lipids and intermediate metabolites (17), protein kinase C activation (18–20), proinflammatory nuclear factor (NF)-kB pathway activation (20–22), and oxidative stress (15,23).”
BackgroundKahn, S. E., Prigeon, R. L., McCulloch, D. K., Boyko, E. J., Bergman, R. N., Schwartz, M. W., Neifing, J. L., Ward, W. K., Beard, J. C., & Palmer, J. P. (1993) · Diabetes · doi:10.2337/diab.42.11.1663 · Cited by 1,405
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
Mechanism by which high-dose aspirin improves glucose metabolism in type 2 diabetes
Hundal, R. S., Petersen, K. F., Mayerson, A. B., Randhawa, P. S., Inzucchi, S., Shoelson, S. E., & Shulman, G. I. (2002) · Journal of Clinical Investigation · doi:10.1172/jci0214955 · Cited by 557
PKC-θ knockout mice are protected from fat-induced insulin resistance
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., et al. (2004) · Journal of Clinical Investigation · doi:10.1172/jci200422230 · Cited by 500
Endoplasmic reticulum stress is reduced in tissues of obese subjects after weight loss
Gregor, M. F., Yang, L., Fabbrini, E., Mohammed, B. S., Eagon, J. C., Hotamisligil, G. S., & Klein, S. (2009) · Diabetes · doi:10.2337/db08-1220 · Cited by 488 · cited 3×
“Furthermore, gastric bypass surgery in obese patients is associated with reduced ER stress in adipose tissues along with weight loss and improved insulin sensitivity (30).”
BackgroundBoden, G., Duan, X., Homko, C., Molina, E. J., Song, W., Perez, O., Cheung, P., & Merali, S. (2008) · Diabetes · doi:10.2337/db08-0604 · Cited by 468
Free fatty acid-induced hepatic insulin resistance: a potential role for protein kinase C-δ
Lam, T. K. T., Yoshii, H., Haber, C. A., Bogdanovic, E., Lam, L., Fantus, I. G., & Giacca, A. (2002) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00038.2002 · Cited by 195
Self-citation
Cited by
Protein misfolding in the endoplasmic reticulum as a conduit to human disease
Wang, M., & Kaufman, R. J. (2016) · Nature · doi:10.1038/nature17041 · Cited by 1,630
Targeting the unfolded protein response in disease
Hetz, C., Chevet, E., & Harding, H. P. (2013) · Nature Reviews Drug Discovery · doi:10.1038/nrd3976 · Cited by 910
Pancreatic β-cells in type 1 and type 2 diabetes mellitus: different pathways to failure
Eizirik, D. L., Pasquali, L., & Cnop, M. (2020) · Nature Reviews Endocrinology · doi:10.1038/s41574-020-0355-7 · Cited by 854
Arruda, A. P., Pers, B. M., Parlakgül, G., Güney, E., Inouye, K., & Hotamisligil, G. S. (2014) · Nature Medicine · doi:10.1038/nm.3735 · Cited by 720
Lotta, L. A., Scott, R. A., Sharp, S. J., Burgess, S., Luan, J., Tillin, T., Schmidt, A. F., Imamura, F., Stewart, I. D., Perry, J. R. B., et al. (2016) · PLOS Medicine · doi:10.1371/journal.pmed.1002179 · Cited by 417
Metadata
- Authors
- Xiao, C., Giacca, A., & Lewis, G. F.
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2011-02-21
- Volume
- 60
- Issue
- 3
- Pages
- 918-924
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2149843865
- Cited by
- 197
- References
- 10
- FWCI
- 8.44
- Type
- journal article
- Language
- en
- Open access
- hybrid
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
How to cite
Cite CoChat for the checks on this page, and the paper for its own findings.
- This page
- CoChat. (2026). Citation check: Sodium Phenylbutyrate, a Drug With Known Capacity to Reduce Endoplasmic Reticulum Stress, Partially Alleviates Lipid-Induced Insulin Resistance and β-Cell Dysfunction in Humans. https://app.cochat.ai/papers/10.2337/db10-1433
- The paper
- Xiao, C., Giacca, A., & Lewis, G. F. (2011). Sodium Phenylbutyrate, a Drug With Known Capacity to Reduce Endoplasmic Reticulum Stress, Partially Alleviates Lipid-Induced Insulin Resistance and β-Cell Dysfunction in Humans. Diabetes. https://doi.org/10.2337/db10-1433
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
