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- Open Access
Inhibition of myostatin signaling increases glucose in insulin-deficient diabetic mice
© Wang et al; licensee BioMed Central Ltd. 2012
- Published: 1 June 2012
- Increase Muscle Mass
- High Blood Glucose Level
- Activin Receptor
Myostatin (MSTN), a TGF-β superfamily member, is a negative regulator of muscle mass that plays an important role in metabolism. Mstn KO mice have increased muscle mass, reduced adipose mass and improved insulin sensitivity. We have recently shown that MSTN inhibition in muscle prevents the development of diabetes in a mouse model of lipodystrophy. Whether inhibition of MSTN in a type I diabetes model would improve hyperglycemia is unknown.
We used streptozotocin (STZ)-treated C57 mice in which the insulin-producing β-cells were specifically damaged leading to hyperglycemia. After overt diabetes developed, the STZ-treated mice were injected with a MSTN inhibitor, a soluble Activin receptor type II B (ACVR2B:Fc). Blood glucose levels were measured regularly by glucometer. Pyruvate tolerance and glutamine tolerance tests were performed and several hormones in the serum were measured. Real-time PCR was used to compare the expression level of some genes involved in gluconeogenesis.
The soluble ACVR2B:Fc-treated STZ mice have higher blood glucose levels compared with untreated STZ mice. There were no differences in insulin and glucagon levels between ACVR2B:Fc treated or untreated STZ mice. However, there were higher levels of the glucocorticoid corticosterone in soluble ACVR2B:Fc-treated mice. Real-time PCR data showed that the expression of the PEPCK gene was increased significantly in ACVR2B:Fc-treated mice.
Our data suggest that the soluble ACVR2B:Fc treatment worsens hyperglycemia possibly due to increased gluconeogenesis. These data suggest that MSTN inhibition will not be useful for treating type I diabetes.
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.