The DOI matches its Crossref record; 38 of the 39 references it cites were found in a registry or an index.
The effects of a soluble activin type IIB receptor on obesity and insulin sensitivity
Open accessAbstract
Background Myostatin, also known as Growth and Differentiation Factor 8, is a secreted protein that inhibits muscle growth. Disruption of myostatin signaling increases muscle mass and decreases glucose, but it is unclear whether these changes are related. We treated mice on chow and high-fat diets with a soluble activin receptor type IIB (ActRIIB, RAP-031), which is a putative endogenous signaling receptor for myostatin and other ligands of the TGF-beta superfamily.Results After 4 weeks, RAP-031 increased lean and muscle mass, grip strength and contractile force. RAP-031 enhanced the ability of insulin to suppress glucose production under clamp conditions in high-fat fed mice, but did not significantly change insulin-mediated glucose disposal. The hepatic insulin-sensitizing effect of RAP-031 treatment was associated with increased adiponectin levels. RAP-031 treatment for 10 weeks further increased muscle mass and drastically reduced fat content in mice on either chow or high-fat diet. RAP-031 suppressed hepatic glucose production and increased peripheral glucose uptake in chow-fed mice. In contrast, RAP-031 suppressed glucose production with no apparent change in glucose disposal in high-fat-diet mice.Conclusion Our findings show that disruption of ActRIIB signaling is a viable pharmacological approach for treating obesity and diabetes.
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“Inhibition of ActRII signaling through genetic deletion of muscle ActRIIA/B, antibody blockade of ActRIIA/B, or treatment with a soluble ActRIIB decoy receptor all lead to significant increases in muscle mass [[15], [16], [17]].”
From Antibody blockade of activin type II receptors preserves skeletal muscle mass and enhances fat loss during GLP-1 receptor agonism (2024) · cites this paper as [15]
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“It is well appreciated that ActRII ligands such as myostatin and activin A negatively regulate muscle size”
From Antibody blockade of activin type II receptors preserves skeletal muscle mass and enhances fat loss during GLP-1 receptor agonism (2024) · cites this paper as [15]
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“ActRII blockade increases muscle size as well as reduces fat mass [15,18]”
From Antibody blockade of activin type II receptors preserves skeletal muscle mass and enhances fat loss during GLP-1 receptor agonism (2024) · cites this paper as [15]
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Metadata
- Authors
- Akpan, I., Goncalves, M. D., Dhir, R., Yin, X., Pistilli, E. E., Bogdanovich, S., Khurana, T. S., Ucran, J., Lachey, J., & Ahima, R. S.
- Affiliations
- University of Pennsylvania Health System (US)
- University of Pennsylvania (US)
- Acceleron Pharma (United States) (US)
- Corresponding author
- Ahima, R S
- Venue
- International Journal of Obesity
- Published
- 2009-08-11
- Volume
- 33
- Issue
- 11
- Pages
- 1265-1273
- ISSN
- 0307-0565 (ISSN-L)
- 1476-5497
- PMC
- PMC2783781
- OpenAlex
- W2050592095
- Cited by
- 140
- References
- 39
- Citations by year
- 2026: 4 · 2025: 1 · 2024: 8 · 2023: 7 · 2022: 4 · 2021: 8 · 2020: 9 · 2019: 6 · 2018: 4 · 2017: 4 · 2016: 7 · 2015: 12 · 2014: 17 · 2013: 12 · 2012: 10
- FWCI
- 8.28
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- International Journal of Obesity (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (P01DK049210, R01DK062348, P30 DK 19525, P30DK019525)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Keywords
- myostatin, obesity, insulin sensitivity, high-fat diet, hepatic glucose production, glucose uptake, muscle mass, adiponectin, TGF-beta superfamily, diabetes mellitus
- MeSH terms
- Animals, Insulin Resistance, Male, Mice, Inbred C57BL, Obesity, Solubility, Glucose Clamp Technique, Signal Transduction, Case-Control Studies, Muscle, Skeletal, Activin Receptors, Type II, Mice, Myostatin
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