Abstract
Hypercatabolism is common under septic conditions. Skeletal muscle is the main target organ for hypercatabolism, and this phenomenon is a vital factor in the deterioration of recovery in septic patients. In skeletal muscle, activation of the ubiquitin-proteasome system plays an important role in hypercatabolism under septic status. Insulin is a vital anticatabolic hormone and previous evidence suggests that insulin administration inhibits various steps in the ubiquitin-proteasome system. However, whether insulin can alleviate the degradation of skeletal muscle protein by inhibiting the ubiquitin-proteasome system under septic condition is unclear. This paper confirmed that mRNA and protein levels of the ubiquitin-proteasome system were upregulated and molecular markers of skeletal muscle proteolysis (tyrosine and 3-methylhistidine) simultaneously increased in the skeletal muscle of septic rats. Septic rats were infused with insulin at a constant rate of 2.4 mU.kg-1.min-1 for 8 hours. Concentrations of mRNA and proteins of the ubiquitin-proteasome system and molecular markers of skeletal muscle proteolysis were mildly affected. When the insulin infusion dose increased to 4.8 mU.kg-1.min-1, mRNA for ubiquitin, E2-14 KDa, and the C2 subunit were all sharply downregulated. At the same time, the levels of ubiquitinated proteins, E2-14KDa, and the C2 subunit protein were significantly reduced. Tyrosine and 3-methylhistidine decreased significantly. We concluded that the ubiquitin-proteasome system is important skeletal muscle hypercatabolism in septic rats. Infusion of insulin can reverse the detrimental metabolism of skeletal muscle by inhibiting the ubiquitin-proteasome system, and the effect is proportional to the insulin infusion dose.
Highlights
Muscle catabolism, resulting in muscle wasting and fatigue, is a characteristic metabolic response to sepsis [1,2,3]
Sepsis-induced muscle catabolism is mainly caused by increased protein breakdown, in particular myofibrillar protein breakdown, reduced protein synthesis and inhibited amino acid transport contribute to the metabolic response
Proteolytic rate in extensor digital longus muscle The proteolytic rate of skeletal muscle was measured as net release of tyrosine for total protein and 3-MH for myofibrillar protein
Summary
Muscle catabolism, resulting in muscle wasting and fatigue, is a characteristic metabolic response to sepsis [1,2,3]. Sepsis-induced muscle catabolism is mainly caused by increased protein breakdown, in particular myofibrillar protein breakdown, reduced protein synthesis and inhibited amino acid transport contribute to the metabolic response. Previous studies provided evidence that sepsis-induced muscle proteolysis is caused by increased protein breakdown, through the ubiquitin (Ub)-proteasome pathway [4,5,6]. In this pathway, Ub, which contains 76 amino. In patients in intensive care unit, insulin administration reduces morbidity by preventing organ failure, as evidenced by a reduction in duration of mechanical ventilation [12]. The molecular mechanism by which insulin suppresses protein degradation remains poorly understood
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call