Systemic response to thermal injury in rats. Accelerated protein degradation and altered glucose utilization in muscle.

Abstract

Abstract. Negative nitrogen balance and increased oxygen consumption after thermal injury in humans and experimental animals is related to the extent of the burn. To determine whether defective muscle metabolism is restricted to the region of injury, we studied protein and glucose metabolism in forelimb muscles of rats 48 h after a scalding injury of their hindquarters. This injury increased muscle protein degradation (PD) from 140±5 to 225±5 nmol tyrosine/g per h, but did not alter protein synthesis. Muscle lactate release was increased >70%, even though plasma catecholamines and muscle cyclic AMP were not increased. Insulin dose-response studies revealed that the burn decreased the responsiveness of muscle glycogen synthesis to insulin but did not alter its sensitivity to insulin. Rates of net glycolysis and glucose oxidation were increased and substrate cycling of fructose-6-phosphate was decreased at all levels of insulin.The burn-induced increase in protein and glucose catabolism was not mediated by adrenal hormones, since they persisted despite adrenalectomy. Muscle PGE2 production was not increased by the burn and inhibition of prostaglandin synthesis by indomethacin did not inhibit proteolysis. The increase in PD required lysosomal proteolysis, since inhibition of cathepsin B with EP475 reduced PD.

Serum enzymes in thermal injury

“…Several experimental studies have shown that thermal injury can result in increased lipid peroxidation mediated by free radicals, which are detectable in burnt skin, lung tissue and plasma (3,6,11). Similar results are reported earlier in human thermal injury (5, 7).…”

“…Systemic changes in enzymes following burn injury has been reported to involve wide number of organs. Most vulnerable organs which succumb to these changes are liver (2), heart (3), pancreas (4), kidneys (5), gastrointestinal tract and Lungs (6).…”

Dichloroacetate inhibits glycolysis and augments insulin-stimulated glycogen synthesis in rat muscle.

“…The intracellular radioactivity was calculated using previously determined values of the water content and extracellular volume of the epitrochlearis muscle (10). Glucose [2-3H]glucose (9). The formation of 3H20 was measured because it is an index ofthe rate ofglucose phosphorylation ( 11) and corresponds closely to glucose uptake by perfused muscle (12 Glucose uptake was calculated as [5-3H]glucose incorporated into glycogen plus 3H20 formed during glycolysis (9).…”

“…Glucose [2-3H]glucose (9). The formation of 3H20 was measured because it is an index ofthe rate ofglucose phosphorylation ( 11) and corresponds closely to glucose uptake by perfused muscle (12 Glucose uptake was calculated as [5-3H]glucose incorporated into glycogen plus 3H20 formed during glycolysis (9). Net glycolysis was calculated as the difference between the rate of 3H20 formed and substrate recycling (15).…”

“…We also found that raising extracellular lactate can inhibit glycolysis so the effect of DCA does not depend on reducing intracellular lactate. Finally, we examined whether DCA would exert the same metabolic effects when the response ofmuscle to a catabolic condition, thermal injury, included accelerated glycolysis and depressed glycogen synthesis (9).…”