The DOI matches its Crossref record; 18 of the 18 references it cites were found in a registry or an index.
Tauroursodeoxycholic Acid May Improve Liver and Muscle but Not Adipose Tissue Insulin Sensitivity in Obese Men and Women
Open accessAbstract
OBJECTIVE: Insulin resistance is commonly associated with obesity. Studies conducted in obese mouse models found that endoplasmic reticulum (ER) stress contributes to insulin resistance, and treatment with tauroursodeoxycholic acid (TUDCA), a bile acid derivative that acts as a chemical chaperone to enhance protein folding and ameliorate ER stress, increases insulin sensitivity. The purpose of this study was to determine the effect of TUDCA therapy on multiorgan insulin action and metabolic factors associated with insulin resistance in obese men and women. RESEARCH DESIGN AND METHODS: Twenty obese subjects ([means ± SD] aged 48 ± 11 years, BMI 37 ± 4 kg/m2) were randomized to 4 weeks of treatment with TUDCA (1,750 mg/day) or placebo. A two-stage hyperinsulinemic-euglycemic clamp procedure in conjunction with stable isotopically labeled tracer infusions and muscle and adipose tissue biopsies were used to evaluate in vivo insulin sensitivity, cellular factors involved in insulin signaling, and cellular markers of ER stress. RESULTS: Hepatic and muscle insulin sensitivity increased by ∼30% (P < 0.05) after treatment with TUDCA but did not change after placebo therapy. In addition, therapy with TUDCA, but not placebo, increased muscle insulin signaling (phosphorylated insulin receptor substrateTyr and AktSer473 levels) (P < 0.05). Markers of ER stress in muscle or adipose tissue did not change after treatment with either TUDCA or placebo. CONCLUSIONS: These data demonstrate that TUDCA might be an effective pharmacological approach for treating insulin resistance. Additional studies are needed to evaluate the target cells and mechanisms responsible for this effect.
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“Subjects randomized to receive TUDCA and placebo were similar in age, sex, BMI, and body composition (Table 1).”
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“It is likely this difference in route of administration further limited the systemic availability of TUDCA in our subjects, because TUDCA is effectively metabolized by the liver and there is minimal splanchnic escape of bile acid conjugates into the systemic circulation (47).”
Background
Cited by
Inflammatory Mechanisms in Obesity
Gregor, M. F., & Hotamisligil, G. S. (2011) · Annual Review of Immunology · doi:10.1146/annurev-immunol-031210-101322 · Cited by 3,754
Self-citationMechanisms for Insulin Resistance: Common Threads and Missing Links
Samuel, V. T., & Shulman, G. I. (2012) · Cell · doi:10.1016/j.cell.2012.02.017 · Cited by 2,294
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
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Self-citationTargeting 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
Metadata
- Authors
- Kars, M., Yang, L., Gregor, M. F., Mohammed, B. S., Pietka, T. A., Finck, B. N., Patterson, B. W., Horton, J. D., Mittendorfer, B., Hotamisligil, G. S., & Klein, S.
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2010-06-03
- Volume
- 59
- Issue
- 8
- Pages
- 1899-1905
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2120242770
- Cited by
- 400
- References
- 18
- FWCI
- 10.51
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Kars, M., Yang, L., Gregor, M. F., Mohammed, B. S., Pietka, T. A., Finck, B. N., Patterson, B. W., Horton, J. D., Mittendorfer, B., Hotamisligil, G. S., & Klein, S. (2010). Tauroursodeoxycholic Acid May Improve Liver and Muscle but Not Adipose Tissue Insulin Sensitivity in Obese Men and Women. Diabetes. https://doi.org/10.2337/db10-0308
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