MECHANISMS REGULATING SKELETAL-MUSCLE GLUCOSE-METABOLISM IN SEPSIS

Carbohydrate dyshomeostasis is a characteristic feature of sepsis. Sep sis elevates glucose uptake and cellular lactate levels in muscle. The mechanisms responsible for these alterations are unknown. We examined the effects of a chronic, intra-abdominal septic abscess upon glucose uptake, the expression of the insulin receptor, glucose transporter p roteins (Glut-1 and Glut-4) and mRNA, and the content of glycolytic in termediates in muscle from the hindlimb. Sepsis caused a 67% increase in glucose uptake compared with control. A differential expression of the Glut-1 and Glut-4 transporter proteins in skeletal muscle of septi c rats was observed. Sepsis increased the expression of Glut-1 protein 1.7-fold. The increased Glut-1 protein correlated with a similar incr ease in the relative abundance of Glut-1 mRNA. In contrast, sepsis did not alter the amount of Glut-4 protein and mRNA or insulin receptor p rotein. The tissue content of glucose-6-phosphate was increased approx imately twofold compared with control. The increase in the glucose-6-p hosphate content was not associated with increased glycogen deposition in skeletal muscle of septic animals. Analysis of the glycolytic inte rmediates showed that only the lactate content of muscles from septic rats was significantly elevated in sepsis. The results are consistent with the hypothesis that sepsis enhances glucose uptake secondary to i ncreased Glut-1 expression. Furthermore, once transported, glucose may be preferentially metabolized to lactate.