Insulin induced hypoglycemia and tolbutamide administration accompanied by much smaller falls in blood glucose were associated with increased pancreatic vein IRG concentrations in laparotomized dogs under barbiturate anesthesia. Hyperglycemia may have diminished pancreatic IRG release. Changes in IRG levels in peripheral and jejunal veins during hypoglycemia were unremarkable. In dogs, pancreatectomy was associated with no change in IRG release into a jejunal vein. Very small doses of glucagon administered intraportally during hyperglycemia were effective in promoting IRI release. It is concluded that a fall in blood glucose from the basal state is a stimulus, and hyperglycemia is an inhibitor, of pancreatic IRG release. It is possible that glucagon may act in the basal state to deliver repeated small pulses of glucose and insulin into the circulation.

No abstract

Niemann Pick type C (NPC) disease is an autosomal recessive disorder characterized by abnormal cholesterol metabolism and accumulation in lysosomal and endosomal compartments. Although peripheral organs are affected, the progressive neurodegeneration in the brain is typically most deleterious, leading to dystonia, ataxia, seizures, and premature death. Although the two genes underlying this disorder in humans and mouse models of the disease have been identified (NPC1 in 95% and NPC2/HE1 in 5% of human cases), their cellular roles have not Been fully defined, and there is currently no effective treatment for this disorder. To help address these issues, we constructed a recombinant adenovirus, Ad(NPC1-GFP), which contains a cDNA encoding a mouse NPC1 protein with a green fluorescent protein (GFP) fused to its C-terminus. Fluorescence microscopy and cholesterol trafficking assays demonstrate that the GFP-tagged NPC1 protein is functional and detectable in cells from different species (hamster, mouse, human) and of different types (ovary-derived cells, fibroblasts, astrocytes, neurons from peripheral and central nervous systems) in vitro. Combined with results from time-lapse microscopy and in vivo brain injections, our findings suggest that this adenovirus offers advantages for expressing NPC1 and analyzing its cellular localization, movement, functional properties, and beneficial effects in vitro and in vivo.

These data suggest a possible role for circulating activated T lymphocytes in the pathogenesis of autoeczematization and possibly in severe psoriasis.

High levels of neutral triglyceride lipase activity have been demonstrated In several types of macrophages (J774 cells, human monocyte/macrophages, rabbit alveolar macrophages, and resident mouse peritoneal macrophages). The pH optima ranged from 6.5 to 7.4 depending upon the buffer and the conditions of incubation. The addition of bovine serum albumin stimulated activity at low concentrations, as expected for a fatty acid-releasing reaction, but strongly inhibited at higher concentrations; maximal activity was observed In the presence of 0.625 mg/ml of bovine serum albumin. The enzyme was remarkably thermostable, showing no apparent loss of activity at 50°C for as long as 6 hours. The lipase was Inhibited 80% by 0.1 M NaCI. Assayed under optimal conditions, the specific activity of the neutral triglyceride lipase from J774 cells was more than 100-fold greater than the activity of llpoproteln lipase or neutral cholesterol esterase from those cells; this activity was 10-fold greater than the levels of hormone- T he lipid that accumulates in eruptive xanthomatosis, mostly triglycerides, is found in histiocytes or foam cells, cells that are probably derived from circulating monocytes.1 In patients with hyperchylomicronemia, these triglyceride-rich cells are found in the spleen and liver as well as in the skin; similar triglyceride-rich cells are seen in severe forms of diabetic-hyperlipemia.2 When the hyperlipemia is brought under control, the eruptive xanthomata may resolve very rapidly, sometimes within a day or two. Serial bfopsy studies by Parker et al. 2 showed that the triglyceride content of the lesions fell much more rapidly than the cholesterol ester content. Electron microscopic studies show that most of the stored lipid in foam cells is contained in cytoplasmic vesicles lacking a limiting membrane.3 A number of lines Received May 12, 1983; revision accepted August 17, 1983. of evidence suggest that these cytoplasmic lipid droplets result from lysosomal degradation of lipids taken up from chylomicrons (and/or very low density lipoproteins) and then are resynthesized in the cytoplasmic compartment from products escaping the lysosome. 4' 5 Mobilization of these lipid stores presumably involves either movement back into the lysosomal compartment for hydrolysis or the action of cytoplasmic hydrolases.Previous studies in this laboratory have demonstrated the presence of a neutral cytoplasmic cholesterol esterase in homogenates of several types of macrophages.6 These cells were also shown to contain and to secrete a lipoprotein lipase similar in most respects to postheparin plasma lipoprotein lipase. 78Being a triglyceride lipase, the latter enzyme might theoretically play a role in the mobilization of stored triglycerides, but lipoprotein lipase in adipose tissue and other tissues functions exclusively in the uptake of plasma lipoprotein triglycerides, not in the mobilization of stored triglycerides. Our initial attempts to demonstrate additional neutral triglyceride lipase activities in macrophages were un...