The role of Salmonella typhimurium endotoxin in producing hypertriglyceridemia was investigated in 70 male rhesus monkeys. Dose-response studies were performed with 0.3-9.0 mg of endotoxin/kg injected intravenously; free fatty acids and triglycerides were measured during the subsequent 8 hr. The effect of endotoxin on lipid disposal mechanisms was assessed by both intravenous lipid-loading tests and total plasma lipolytic activity after administration of heparin. The possible interference of endotoxin with lipid-clearing enzymes was also explored. Smaller doses of endotoxin (0.3 and 0.9 mg/kg) produced significant increments in free fatty acids within 2-5 hr of administration, with minimal trilgyceride increments. Larger doses of endotoxin (2.8-9.0 mg/kg) failed to produce significant elevations in free fatty acids but did result in significant triglyceride increases 2-6 hr after administration. Within 4 hr after administration of 7 mg of endotoxin/kg, both tests showed impaired disposal of lipids. However, once lipid-clearing enzymes were activated, endotoxin did not reduce lipolytic activity in vitro. These results support the contention that endotoxin significantly elevates serum triglyceride concentrations and leads to impaired lipid disposal mechanisms by interfering with the activation of lipid-clearing enzymes.

To characterize further the role of blood cells in amino acid transport, four normal volunteers were asked to ingest 200 g of broiled ground sirloin within a 10-min period. Blood samples from a radial artery, a deep vein draining forearm muscle bed, and a tributary of the hepatic vein were obtained prior to and for 4 hr after the meal and analyzed for various hormones and substrates. At rest, analysis of arterio-deep venous differences across the forearm revealed the blood cell and plasma amino acid compartmentmental contents to be relatively constant except for alanine and glutamine. Whole blood arterio-hepatic venous (A-HV) amino acid differences were not significantly different from zero; however, blood cell A-HV difference analysis revealed a significant release of threonine from the splanchnic bed while plasma A-HV difference analysis revealed modest but significant releases of glutamate and ornithine and uptakes of phenylalanine and histidine. After the ingestion of the meat meal, plasma and blood cell levels of almost all of the measured amino acids increased significantly. Notable exceptions included glycine and alanine, levels of which did not change significantly and glutamine. The arterial blood cell content of the latter amino acid paradoxically decreased while arterial plasma levels increased significantly. Most importantly, large quantities of branched chain amino acids were released from the splanchnic bed and removed by forearm muscle. These data suggest that the blood cells of normal man do actively participate in amino acid transport, and that the magnitude and direction of change induced by the ingestion of a proteins meal varies with the individual amino acid.

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To detect abnormalities in the secretion of insulin and growth hormone in monozygotic twin siblings of patients with juvenile-onset diabetes, their responses during oral, cortisone-primed oral, and intravenous, glucose tolerance tests and intravenous tolbutamide tests were compared to those of matched controls. The twins had higher mean serum insulin levels during all tests, but differences reached statistical significance (P less than 0.02) only in the cortisone-primed test. Growth hormone levels were higher in the twins (P less than 0.04) in the intravenous tolbutamide tolerance test. The frequency of abnormal oral glucose tolerance tests among controls, diabetic monozygotic twins and the offspring of two diabetic parents was also compared. Twins and controls had nearly the same frequency of normal tests; however, the diabetic offspring had a significantly higher (P less than 0.001) prevalence of abnormal tests. These data suggest that magnitudes of environmental and genetic factors operating in monozygotic "pre-diabetic" children of diabetic parents.

Eight male patients with cystic fibrosis, normal nutrition, normal physical activity, relatively mild pulmonary disease, no evidence of liver disease and no family history of diabetes mellitus underwent a series of carbohydrate tolerance tests in comparison with a group of 18 normal male subjects matched for age and body weight. Compared with the normal group, the patients with cystic fibrosis had significantly impaired glucose tolerance and significantly lower serum immunoreactive insulin levels during oral and intravenous glucose tolerance tests; serum insulin levels were also significantly lower after intravenous administration of tolbutamide in the patients with cystic fibrosis, but the reduction in blood glucose concentration in each group was not significantly different. During an intravenous insulin test, the decrease in blood glucose concentration was the same for both groups, in spite of significantly lower serum insulin levels in the patients with cystic fibrosis. The percentage fall in plasma free fatty acids was at least as great in the patients with cystic fibrosis as in normals during the test procedures, while a significant decrease in plasma alpha-amino nitrogen after intravenously administered insulin was seen only in the patients with cystic fibrosis. These studies suggest that the carbohydrate intolerance of cystic fibrosis is consequent upon an impaired insulin response to glucose, but that this insulin deficiency is partly compensated for by increased peripheral tissue sensitivity to insulin.