Inhibitory effects of exogenous insulin on oxidative utilization of glucose in septic rats.

The influence of exogenous insulin on oxidation of U-14C-glucose was investigated by monitoring the production of 14CO2 in septic rats. Ten Wistar rats underwent ligation of the distal third of the caecum and the ligated caecum was punctured with a 21-G needle (septic rats: group S). A group of ten rats was not subjected to these procedures (control rats: group C). Both groups received parenteral nutrition (PN) for the subsequent 27 hours. Non-protein nutrients were provided exclusively as glucose. Five rats in each group received insulin at a rate of 0.64 U/kg/hr for the last six hours of PN, and these rats were designated groups CI and SI. At the 21st hour of PN, 1.563 muCi of U-14C-glucose was injected as a bolus, and the production of 14CO2 was measured. The cumulative production of 14CO2 for the subsequent six hours, given as a percentage of the 14C injected, was 78.22 +/- 6.22% in group C, 86.16 +/- 4.23% in group CI, 62.38 +/- 13.00% in group S, and 54.38 +/- 6.89% in group SI. The elevated levels of blood glucose in rats in group S were reduced by the administration of insulin. These results indicate that the reduction of elevated blood glucose levels by exogenous insulin in the septic rats with antecedent hyperinsulinemia does not reflect an increase in the oxidative utilization of glucose but rather inhibition of the oxidation of glucose.

[Effects of exogenous insulin on oxidation of glucose and fatty acid in septic rats].

The effects of exogenous insulin on oxidation of glucose and fatty acid were investigated in septic (n = 20) and control rats (n = 20). Sepsis was induced by ligation and puncture of the caecum. The rats received intravenous nutrition with glucose as a non-protein calorie for 27 hours. Ten rats in each group received insulin intravenously at a rate of 0.64U/kg/hr during the last 6 hours of the intravenous nutrition, U-14C-glucose or 1-14C-linoleic acid at a dose of 1.563 microCi each was injected as a bolus at the 21st hour of the intravenous nutrition. Cumulative 14CO2 production was measured for 6 hours after the injection of the radioactive substrates. 14CO2 production from both glucose and linoleic acid was inhibited by the sepsis. 14CO2 production from glucose was accelerated by exogenous insulin in the control rats, while it was not accelerated in the septic rats. Exogenous insulin did not affect 14CO2 production from linoleic acid in both the control and the septic rats. These results indicate that, under the condition of sepsis, lowering blood sugar level with exogenous insulin does not refLect an increase in oxidation of glucose.

Influences of an infusion of lipid emulsion on phagocytotic activity of cultured Kupffer's cells in septic rats.

An experimental study was undertaken to study the influences of an infusion of lipid emulsion on phagocytosis of Kupffer's cells in septic rats. Sepsis was induced in 13 rats by ligating the cecum. Five of them received glucose as the sole nonprotein calorie (septic-glucose group), four of the rats received 25% of the nonprotein calorie with lipid emulsion, Intralipid (septic-lipid group), and the remaining four rats did not receive any intravenous solution and were allowed access to water (septic-fasted group). Another four rats which received neither intravenous solution nor ligation of the cecum served as the control group. The intravenous infusion was carried out for 72 hr. The phagocytotic activity of Kupffer's cells was determined by the ability to engulf latex particles with a size of 1.09 micron, in vitro. The phagocytotic activity was enhanced by the presence of sepsis but it was inhibited by starvation. The difference in the phagocytotic activity between the septic-glucose group and the septic-lipid group was not significant. These results suggest that, insofar as an in vitro study is concerned, a 72-hr infusion of lipid emulsion at a rate of 25% of the total nonprotein calorie does not influence the phagocytotic activity of cultured Kupffer's cell obtained from septic rats.

Effects of total parenteral nutrition on the development of intestinal endotoxemia in rats: a comparison between glucose and lipid.

The effects of parenteral nutrition (PN) and of the difference in the PN regimens between glucose and lipid emulsion on the development of endogenous endotoxemia were studied in 40 Wister rats. Endotoxemia was induced by occluding the superior mesenteric vein (SMV) for 30 min. The plasma endotoxin in the portal blood at the time of the release of the SMV occlusion and that in the arterial blood 10 min after the release were quantified. Twenty of the 40 rats had received PN for 48 hr prior to the SMV occlusion. Ten of these 20 rats received the total nonprotein calorie (TNPC) solely with glucose, and the other 10 rats received 25% of the TNPC with lipid emulsion. Ten rats had been allowed free access to lab food until the SMV occlusion. The remaining 10 rats underwent neither the SMV occlusion nor PN, and served as the control group. Both the portal and the arterial endotoxin increased after the release of the SMV occlusion, however the portal endotoxin was higher than that of the arterial one. Both the portal and the arterial endotoxin of the rats supported by PN were significantly lower than those of the rats nourished by lab food, while they were higher than the control values. The difference in the PN regimens did not cause any alteration in the endotoxin levels. These results indicate that the development of intestinal endotoxemia was not influenced by the difference in the PN regimens, but it was rather influenced by a presence of intestinal content.