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Updated: Jun 21, 2026
Differentiated Mouse Adipocytes in Primary Culture: A Model of Insulin Resistance
Published on: February 17, 2023
The effects of a soluble activin type IIB receptor on obesity and insulin sensitivity
I Akpan1, M D Goncalves, R Dhir
1University of Pennsylvania School of Medicine, Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, Philadelphia, PA 19104, USA.
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.
Insights
Disrupting myostatin signaling with RAP-031 increases muscle mass and improves glucose regulation. This approach shows promise for treating obesity and diabetes by enhancing insulin sensitivity and reducing fat content.
Area of Science:
- Muscle physiology
- Metabolic disease research
- Pharmacological interventions
Background:
- Myostatin (Growth and Differentiation Factor 8) inhibits muscle growth.
- The relationship between myostatin inhibition, muscle mass, and glucose metabolism is not fully understood.
- Soluble activin receptor type IIB (ActRIIB, RAP-031) targets myostatin signaling.
Purpose of the Study:
- To investigate the effects of disrupting myostatin signaling on muscle mass and glucose metabolism.
- To determine if ActRIIB inhibition impacts insulin sensitivity in mice on different diets.
Main Methods:
- Mice on chow and high-fat diets were treated with RAP-031.
- Muscle mass, strength, and glucose metabolism were assessed under clamp conditions.
- Adiponectin levels and hepatic glucose production were measured.
Main Results:
- RAP-031 increased lean mass, muscle mass, grip strength, and contractile force.
- Treatment improved insulin's ability to suppress glucose production in high-fat fed mice, associated with increased adiponectin.
- Longer treatment reduced fat content and suppressed hepatic glucose production, with varied effects on glucose disposal based on diet.
Conclusions:
- Disruption of ActRIIB signaling is a viable strategy for treating obesity.
- This approach offers a potential pharmacological treatment for diabetes.
- ActRIIB inhibition impacts both muscle and metabolic pathways.
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