PTEN Expression Contributes to the Regulation of Muscle Protein Degradation in Diabetes

Indiana University-Purdue University Indianapolis, Indianapolis, Indiana, United States
Diabetes (Impact Factor: 8.1). 11/2007; 56(10):2449-56. DOI: 10.2337/db06-1731
Source: PubMed


Conditions accelerating muscle proteolysis are frequently associated with defective phosphatidylinositol 3-kinase (PI3K)/Akt signaling and reduced PI3K-generated phosphatidylinositol 3,4,5-triphosphate (PIP(3)). We evaluated the control of muscle protein synthesis and degradation in mouse models of type 1 and 2 diabetes to determine whether defects besides PI3K/Akt activities affect muscle metabolism.
We evaluated the expression and activity of PTEN, the phosphatase converting PIP(3) to inactive phosphatidylinositol 4,5-bisphosphate, and studied how PTEN influences muscle protein in diabetic wild-type mice and in mice with partial deficiency of PTEN(+/-).
In acutely diabetic mice, muscle PTEN expression was decreased. It was increased by chronic diabetes or insulin resistance. In cultured C2C12 myotubes, acute suppression of PI3K activity led to decreased PTEN expression, while palmitic acid increased PTEN in myotubes in a p38-dependent fashion. To examine whether PTEN affects muscle protein turnover, we studied primary myotubes cultures from wild-type and PTEN(+/-) mice. The proteolysis induced by serum deprivation was suppressed in PTEN(+/-) cells. Moreover, the sizes of muscle fibers in PTEN(+/-) and wild-type mice were similar, but the increase in muscle proteolysis caused by acute diabetes was significantly suppressed by PTEN(+/-). This antiproteolytic response involved higher PIP(3) and p-Akt levels and a decrease in caspase-3-mediated actin cleavage and activation of the ubiquitin-proteasome system as signified by reduced induction of atrogin-1/MAFbx or MurF1 (muscle-specific RING finger protein 1).
Changes in PTEN expression participate in the regulation of muscle proteolytic pathways. A decrease in PTEN could be a compensatory mechanism to prevent muscle protein losses.

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Available from: Jie Du, Feb 04, 2014
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