Effect of Lipopolysaccharide on Skeletal Muscle Functions (LPS)

• Skeletal Muscle Protein Turnover (muscle tracer incorporation) [ Time Frame: 4 hr following LPS infusion ] [ Designated as safety issue: No ]
  

• Whole body glucose disposal [ Time Frame: 4 h Glucose insulin clamp ] [ Designated as safety issue: No ]
  
• Expression of genes that regulate muscle protein balance and insulin signalling [ Time Frame: 4 h following LPS infusion ] [ Designated as safety issue: No ]
  

Biological: Lipopolysaccharide infusion
Lipopolysaccharide 4 nanogram/kg body weight
Other Name: Endotoxin

During sepsis, the ability of the body to prevent muscle wasting is impaired resulting in loss of skeletal muscle. In addition, skeletal muscle handling of carbohydrate becomes less efficient. These changes could result in delayed recovery, prolonged rehabilitation and in severe cases mortality of patients. It is still unclear how these changes occur in the human skeletal muscles but animal experiments suggest that protein molecules that are released during sepsis are responsible for these changes. Due to the biological differences between animals and humans in metabolic rate and stability, disease susceptibility and response to infection, simple translation of knowledge from animals to patients could be highly misleading. Therefore, we aim to examine how the skeletal muscles of the human volunteers respond to experimental septic conditions.

Following medical screening, six healthy men aged 18-30 will have two metabolic study visits in a random manner. On the first visit, while resting on a bed, they will have four cannulae inserted including one in the upper thigh, for blood sampling and the infusion of insulin, glucose and normal and tracer amino acids (which allow us to measure muscle protein metabolism). Subjects will receive either injection of purified bacterial product called lipopolysaccharide (LPS) to induce flu-like symptoms or normal saline according to randomization followed by a metabolic test to stimulate muscle synthesis and glucose transport. Three small samples of muscle will be obtained under local anaesthetic from the thigh to measure molecular events in muscle. By performing these measurements, we will determine the consequences of LPS on muscle production and carbohydrate metabolism.