Analysis of postburn insulin unresponsiveness in skeletal muscle

Three days after a one hindlimb scald in the rat, soleus muscle from the burned limb, but not from the contralateral unburned limb, fails to increase its rate of glucose incorporation into glycogen in response to insulin stimulation in vitro. Data presented indicate that the lack of response to insulin is not due to a release by thermally injured muscle of a substance that would either degrade insulin or decrease its biological potency. The insulin resistance is also not related to morphological changes in muscle because it is exhibited both by the portion of muscle that shows inflammatory and degenerative changes, and the portion of muscle that is electronmicroscopically indistinguishable from normal tissue. The insulin unresponsiveness cannot be reversed by addition of the ATP · MgCl₂ complex. The binding of insulin to its receptors in the intact soleus muscle from the burned limb does not differ from controls at 0.1 and 1.0 mU insulin/ml medium and is only 33% lower at 10 mU insulin/ml. This change in the capacity of thermally injured muscle to bind insulin is not of a sufficient magnitude to account for the complete lack of response to the hormone. Since in the absence of insulin, soleus muscle from the burned limb can convert glucose to glycogen and can respond to increased substrate availability by augmenting glycogen synthesis, the failure of muscle underlying the burn wound to respond to insulin appears to be due to a defect in coupling of the insulin receptor with intracellular effectors and/or in a component of the complex enzymatic machinery regulating glycogen metabolism.