Reversal of Insulin Resistance by ATP in Hemorrhagic Shock

Abstract

Hemorrhagic shock was produced by bleeding rats to a mean arterial pressure of 40 mm Hg (1 mm Hg = 133 N/m2), which was maintained for 2 h. Muscles from these animals ('shock' muscles) showed resistance to the stimulation of glucose uptake by insulin. Addition of 1 mM ATP–MgCl2 to the medium had no effect on basal glucose uptake in either group of muscles, but it permitted insulin to exert its stimulatory effect in 'shock' muscles. An optimal insulin effect on glucose uptake in 'shock' muscles incubated without ATP was observed at an insulin concentration of 0.2 Unit/ml. When 1 mM ATP–MgCl2 was added to the medium, optimal insulin effect in 'shock' muscles was observed at an insulin concentration of 0.007 Unit/ml. Increasing the concentration of ATP–MgCl2 to 2.5 mM in the medium resulted in an optimal insulin effect at an insulin concentration of 0.001 Unit/ml in 'shock' muscles. Following 1 h incubation in Krebs–HCO3 medium, intracellular ATP contents of 'shock' muscles were approximately 50% lower than in control muscles. Addition of 1 mM ATP–MgCl2 to the incubation medium had no effect on the intracellular ATP contents of either group of muscles following incubation; however, 2.5 mM ATP–MgCl2 elevated intracellular ATP contents of 'shock' muscles but had no effect in control muscles. Possible mechanisms for this reversal of insulin resistance by ATP-MgCl2 in shock are discussed.