Glucose utilization by Kupffer cells, endothelial cells, and granulocytes in endotoxemic rat liver.

There are several types of glucose-consuming, immunologically active nonparenchymal cells interspersed among the glucose-producing parenchymal liver cells. Combining the in vivo 2-deoxyglucose tracer technique with cell separation methods enabled us to investigate the effect of Escherichia coli endotoxin on the rate of glucose utilization by the nonparenchymal cells. Rats were injected with [14C]deoxyglucose, and intracellular 2-deoxyglucose 6-phosphate was determined in different liver cell fractions. Parenchymal, Kupffer, and endothelial cells as well as polymorphonuclear leukocytes (PMN) were separated from the liver by centrifugal elutriation followed by Ficoll-Hypaque density gradient. The number of PMN obtained from the liver was increased severalfold 3 h after endotoxin and was comparable to the number of Kupffer cells. Glucose utilization by the liver of fasted rats was due predominantly to nonparenchymal cells. Endotoxin enhanced the rate of glucose utilization by Kupffer (6.7-fold) and endothelial (2.7-fold) cells and by the infiltrated hepatic PMN (5.4-fold). Enhanced glucose metabolism of immunologically active cells is part of the hepatic immune response and subserves the antibacterial defense of the body. The activated cells, however, may also have the potential of causing tissue damage by releasing harmful toxic metabolites.

Superoxide anion generation in the liver during the early stage of endotoxemia in rats.

Infiltration of polymorphonuclear neutrophils (PMN) in the rat liver 3 hr after an intravenous (IV) injection of a sublethal dose of Escherichia coli lipopolysaccharide (LPS) was observed without any significant alteration in the total number of Kupffer and endothelial cells. Since previous studies have demonstrated that phagocytic cells in the liver were in a state of metabolic activation under similar experimental conditions, we investigated the in vitro generation of superoxide anion (O2-) by this cell type following the administration of LPS. Kupffer cells from normal rats did not release O2-, in contrast to those obtained from LPS-treated rats. The generation of O2- by Kupffer cells from endotoxic rats was elevated from 3.0 +/- 1.9 nmol/10(6) cells/60 min (mean +/- SD) in the absence of macrophage (M phi) activators, to 5.0 +/- 2.36, 11.33 +/- 5.40, and 4.33 +/- 0.90 in the presence of opsonized zymosan, phorbol myristate acetate (PMA), and the calcium ionophore A23187, respectively. Hepatocytes from normal or endotoxic rats did not produce detectable O2-. Endothelial cells from LPS-treated rats generated less than 0.8 nmol/10(6) cells in the presence of zymosan. PMN that accumulated in the livers of endotoxic rats released O2- only in the presence of zymosan (8.12 +/- 5.40), PMA (15.43 +/- 5.84), or A23187 (1.70 +/- 0.12). The O2- generation by blood monocytes and PMN increased significantly after endotoxin administration and in the presence of activators. These results suggest that the hypermetabolic state of phagocytic cells in the liver shortly after LPS treatment may be correlated with the increased generation of O2-. The latter may subsequently contribute to the induction of hepatic injury in endotoxemia.

Early changes in glucose utilization of individual tissues after endotoxin administration.

Administration of Escherichia coli endotoxin (100 micrograms/100 g, i.v.) to conscious rats induces transient hyperglycemia and a sustained increase in whole body glucose turnover. To identify the tissues responsible for the increase in glucose utilization, the glucose metabolic rate (Rg) of peripheral tissues was determined in vivo by the 2-deoxyglucose tracer technique during and after the hyperglycemic phase. Rg was markedly increased in spleen, liver, intestine, epidydimal fat, gastrocnemius muscle, and skin during the early hyperglycemic period (80 min after endotoxin) and remained elevated in the subsequent euglycemic period (220 min). Combined alpha- and beta-adrenergic blockade, achieved by the primed continuous infusion of phentolamine and propranolol, prevented the transient hyperglycemia that followed endotoxin injection. Adrenergic blockade also prevented or considerably attenuated the early increases in tissue glucose utilization that were induced by endotoxin. The results indicate that the early increase in Rg can be mainly attributed to adrenergic stimulation and the resultant hyperglycemia, while the sustained elevation is due to mechanisms independent of hyperglycemia.

Use of an artificial endocrine pancreas in diabetic pregnancy.

Insulin demand of 12 pregnant diabetics has been investigated with an artificial endocrine pancreas. A rise in insulin requirement during pregnancy which can be attributed to the effort of reaching normoglycemia and to the effect of contrainsular hormones has also been observed by this objective method. Assessment of basal insulin demand during the night might be helpful in optimizing conventional therapy by using long-acting insulins for supplementing basal insulin need. According to our results, pregnancy complicated by diabetes can be foreseen as one of the main applications of a glucose-controlled insulin infusion system.

Study on the insulin-binding capacity of blood serum by a cellulose adsorption method.

The cellulose adsorption method was used for the quantitative study of the insulin-binding capacity of blood serum. The results support the view that anti-bodies to insulin are of exogenous origin and that may be responsible for insulin resistance in individual cases. While the insulin requirement of patients was found to be related to the serum antibody level, the latter was unaffected by the duration of insulin treatment even though the number of cases exhibiting normal values decreased with the length of treatment.