Alterations in tissue glucose uptake during the hyperglycemic and hypoglycemic phases of sepsis

The purpose of the present study was to characterize the alterations in tis sue glucose uptake during the hyperglycemic, euglycemic, and hypoglycemic p hases of peritonitis. Rats had vascular catheters implanted, and sepsis was induced by cecal ligation and puncture. Rates of whole-body glucose appear ance (Ra), disappearance (Rd), and metabolic clearance (MCR) were determine d by the constant infusion of H-3-glucose, and in vivo glucose uptake (Rg) by individual tissues was assessed by using C-14-deoxyglucose. During the h yperglycemic phase of sepsis (2 h), glucose Ra and Rd were increased, but g lucose MCR was unaltered. in contrast, during the euglycemic phase (6 h), t he sepsis-induced increase in glucose Ra and Rd was associated with an elev ation in the MCR. Finally, during the hypoglycemic phase (24 h), sepsis dec reased glucose Ra and Rd and the glucose MCR. The sepsis-induced changes in Rg for skeletal muscle and adipose tissue mimic those seen for the whole b ody at each time point. Rg for skin and intestine was elevated at 2 h and 6 h but was not different from control values at 24 h. In contrast, the Rg f or liver, lung, and spleen was increased at all 3 time points. In a second study, there was no difference in Rg for any tissue between 2-h septic rats and control animals in which blood glucose and insulin levels were artific ially elevated to the same degree, in a third study, the prevailing glucose and insulin levels in control animals were decreased, by injection of the gluconeogenic inhibitor 3-mercaptopicolinic acid, to levels seen in 24-h se ptic rats. There was no difference in the Rg for muscle and adipose tissue between 24-h septic rats and hypoglycemic insulinopenic control animals. Ho wever, the Rg for liver, lung, and spleen remained elevated in 24-h septic rats, compared with hypoglycemic insulinopenic control values. These data i ndicate that the increased tissue glucose uptake observed during the early phase of sepsis is a consequence of concomitant changes in plasma glucose a nd insulin. In contrast, during the euglycemic and hypoglycemic stages of s epsis, glucose uptake in macrophage-rich tissues remains elevated and is in dependent of changes in glucose and insulin.