The effects of a soluble activin type IIB receptor on obesity and insulin sensitivity

I. Akpan, M. D. Goncalves, R. Dhir, X. Yin, E. E. Pistilli, S. Bogdanovich, T. S. Khurana, J. Ucran, J. Lachey, R. S. Ahima

Research output: Contribution to journalArticle

Abstract

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-Β 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.

Original languageEnglish (US)
Pages (from-to)1265-1273
Number of pages9
JournalInternational Journal of Obesity
Volume33
Issue number11
DOIs
StatePublished - Aug 12 2009
Externally publishedYes

Keywords

  • Activin receptor
  • Glucose
  • Insulin
  • Mice
  • Muscle
  • Myostatin

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Endocrinology, Diabetes and Metabolism
  • Nutrition and Dietetics

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    Akpan, I., Goncalves, M. D., Dhir, R., Yin, X., Pistilli, E. E., Bogdanovich, S., Khurana, T. S., Ucran, J., Lachey, J., & Ahima, R. S. (2009). The effects of a soluble activin type IIB receptor on obesity and insulin sensitivity. International Journal of Obesity, 33(11), 1265-1273. https://doi.org/10.1038/ijo.2009.162