Focal differences in lipid metabolism of the young pig aorta. IV. Influence of insulin and epinephrine on lipogenesis from (14C)-U-glucose.

We have previously demonstrated that focal areas of the normal young pig aorta, identified by their ability to take up the protein-binding azo dye Evans Blue, and characterized by an increased endothelial permeability to proteins, exhibit a variety of differences in lipid metabolism, relative to adjacent tissue showing no dye uptake. It was the purpose of the present study to examine the influence of insulin and epinephrine on lipogenesis from [¹⁴C]-U-glucose in these blue and white areas. In white areas, insulin at 25 μU/ml significantly stimulated incorporation of labelled glucose into phosphatidyl choline. By contrast, insulin did not significantly influence glucose incorporation into any lipid examined in adjacent blue areas. In fact, incorporation of [¹⁴C]-U-glucose into blue area lipids was unmodified by insulin at concentrations as great as 10,000 μU/ml. Insulin did not influence the uptake of [¹⁴C]-1-l-Arabinose or [¹⁴C]-U-sucrose in either blue or white areas suggesting that:—(1) insulin-stimulated lipogenesis in white areas is not accompanied by increased glucose uptake and (2) the difference in lipogenic response to insulin between blue and white areas is not due to an insulin-mediated difference in glucose uptake. Epinephrine, in contrast to insulin, did not influence lipogenesis in either blue or white areas.These studies indicate that, in addition to the focal differences in lipid metabolism previously demonstrated, there are also focal differences in the regulation of lipid metabolism in the macroscopically normal young pig aorta. These focal medial metabolic differences, together with differences in the regulation of aortic lipid metabolism may be secondary to the greater trans-endothelial influx of plasma constituents in blue areas. Their role, if any, in the early phases of atherogenesis needs clarification.     

The behavior of (14C)-D-penicillamine in collagen metabolism.

The most important effect of penicillamine on collagen metabolism is the reduction of collagen crosslinking. However, even after long time application of penicillamine, collagen is crosslinked to a certain degree. After intravenous injection of a trace dose of (14C) labelled D-penicillamine it can be determined that this substance is rapidly bound to neutral salt soluble, acetic acid soluble and urea soluble collagen fractions and to a lesser extent to insoluble collagen as well. The amount of penicillamine which binds to any of the collagen fractions depends on the turnover rate. When different tissues are compared, penicillamine seems to have the greatest affinity to tissues with a high collagen turnover. Further studies of neutral salt soluble collagen by CM-cellulose chromatography revealed a stable linkage of penicillamine to collagen alpha chains.     

The synthesis of lipids from [1-14C]acetate by isolated rat brain capillaries

Lipid biosynthesis was investigated in isolated cerebral microvessels obtained from adult Sprague-Dawley rats using [1-14C]acetate as precursor. All lipid classes were labelled by [1-14C]acetate. Neutral lipids incorporated about 50% of radiolabelled acetate, among which free fatty acids and triglycerids showed the highest level of incorporation. Moreover, about 4% of radioactivity was found in cholesterol fraction. In phospholipid fraction, phosphatidylcholine and phosphatidylethanolamine were the main radiolabelled phospholipids. [1-14C]acetate was also incorporated into sulphatides and cerebrosides. The presence of bovine serum albumin in incubation medium modified the percentage of incorporation in different lipid fractions.     

Setaria cervi: lipid biosynthesis from C14-labelled acetate and glucose in the two sexes and microfilariae

Microfilariae (mf), males and females of Setaria cervi were able to synthesize several important classes of lipids and thus exhibited a functional lipid metabolism. The incorporation of the C14 label from acetate into lipids was relatively greater than that from glucose in adults, whereas label from glucose was incorporated to a greater extent in mf. Though only a small portion of these precursors, was utilized for the non-polar (NP) lipid synthesis, they were the preferred substrate for the polar lipid (P) synthesis; the P/NP ratios being 5.2 (mf), 1.63 (male) and 5.16 (female) for acetate and 1.23 (mf), 1.06 (male) and 2.25 (female) for glucose.     

Tissue levels of (3(-14)C) coumarin in the rat: distribution and excretion.

The benzo-pyrones (including coumarin) are a very effective therapy for mild thermal oedema and cases of acute and chronic lymphoedema. In this preliminary report the distribution of a single injected dose of coumarin was followed in normal tissues of rats for 100 hours. Comparisons are to be made later with drug levels in thermally injured and lymphoedematous tissues. The resluts show 7-4% of the injected dose to remain in the tissues after 100 h. During this time 30-9% was excreted in the faeces and approximately 47% excreted in the urine. At any given time most of the dose was present in the gut, muscular tissues, skin and liver. For the gut tissues this was 33%, for the muscular tissues 28%, for the skin 18% and for the liver 16%. The highest concentrations per gram of tissue were however in the kidney and liver, representing the two organs of metabolism and excretion of the coumarin.     

Effect of insulin and its derivatives on incorporation of [1-14C]glycine into tissue proteins

The effect of parenteral injections of insulin and its polypeptide A and B chains on the rate of protein metabolism in various organs of rats was investigated. Insulin was shown to accelerate the incorporation of [1-¹⁴C]glycine into proteins of the liver, kidneys, pancreas, spleen, skeletal muscle, and thyroid, thymus, and adrenal glands but to have no action on this process in heart muscle and the diaphragm. The A and B chains of insulin also activate protein synthesis in several organs. However, despite some specificity of their effect, the spectrum of their action is narrower than that of insulin.A. V. Vishnevskii Institute of Surgery, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR M. I. Kuzin). Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 85, No. 4, pp. 419–421, April, 1978.     

The effect of isoflavones extracted from red clover (Rimostil) on lipid and bone metabolism.

OBJECTIVE: This study was undertaken to evaluate the effects of varying doses of phytoestrogens on lipid and bone metabolism in postmenopausal women. DESIGN: A novel red clover isoflavone preparation (Rimostil) containing genistein, daidzein, formononetin, and biochanin was administered to 46 postmenopausal women in a double-blind protocol after a single-blind placebo phase and followed by a single-blind washout phase. Patients were randomized to receive either 28.5 mg, 57 mg, or 85.5 mg of phytoestrogens daily for a 6-month period. RESULTS: At 6 months, the serum high-density lipoprotein cholesterol had risen significantly by 15.7-28.6% with different doses (p = 0.007, p = 0.002, p = 0.027), although the magnitude of the response was independent of the dose used. The serum apolipoprotein B fell significantly by 11.5-17.0% with different doses (p = 0.005, p = 0.043, p = 0.007) and the magnitude of the response was independent of the dose used. The bone mineral density of the proximal radius and ulna rose significantly by 4.1% over 6 months with 57 mg/day (p = 0.002) and by 3.0% with 85.5 mg/day (p = 0.023) of isoflavones. The response with 28.5 mg/day of isoflavones was not significant. There was no significant increase in endometrial thickness with any of the doses of isoflavone used. CONCLUSION: These results show that the administration of an isoflavone combination extracted from red clover was associated with a significant increase in high-density lipoprotein cholesterol, a significant fall in apolipoprotein B, and a significant increase in the predominantly cortical bone of the proximal radius and ulna after 6 months of treatment. Interpretation of the results is undertaken cautiously because of the absence of a simultaneously studied control group.     

Gastric carcinoma in the young (review of 14 cases)

A retrospective study of 14 cases of gastric carcinoma in the age group of 19 to 35 years is presented. The relevant literature has been reviewed.     

Lipid Biosynthesis from DL (2-14C) Mevalonic Acid in Intact Mice and Rabbits

DL-mevalonate-2-¹⁴C was administered parenterally to 2 rabbits and 5 groups of mice. In the rabbits the amount of labelled material recovered in the non-saponifiable lipids of the kidneys exceeded that of the liver. Most of the renal radioactivity was found in the squalene, lanosterol and methostenol fractions whereas the major part of the labelled material in the liver was present as radioactive cholesterol. The distribution of radioactivity within the kidney and the liver in the mice varied with the size of the administered dose. The smaller the dose, the larger the proportion of label recovered in the kidneys. In all experiments most of the radioactivity of the liver was transformed to cholesterol. The conversion of squalene to cholesterol proceeded more slowly in the kidneys and 30 min after the administration of the mevalonate substantial amounts of radioactivity was recovered as labelled squalene and lanosterol. The importance of circulating mevalonate as substrate in the cholesterol synthesis of the kidney will be discussed.     

pH gradients in the developing teeth of young mice from autoradiography of [14C]DMO.

The distribution of the weak acid [14C]DMO was studied in mice, 10-19 days old, by an autoradiographic technique that does not translocate or remove the compound. Calculations of pH values in areas of the developing teeth of these animals were made by comparing the photometric density of the distribution of [14C]DMO, as an indicator of pH, with that of 14C]NAAP, as an indicator of water content, which was reported in the companion paper. The cellular layers, i.e., odontoblasts, ameloblasts, etc., had pH values of 7.1 +/- 0.1; the pH values in enamel, predentine, and dentine ranged from 7.3 to 8.5. It is suggested that an alkaline matrix promotes nucleation and growth of hydroxyapatite.     

Application of hyperpolarized [1-(13) C]lactate for the in vivo investigation of cardiac metabolism

In addition to cancer imaging, ¹³C‐MRS of hyperpolarized pyruvate has also demonstrated utility for the investigation of cardiac metabolism and ischemic heart disease. Although no adverse effects have yet been reported for doses commonly used in vivo, high substrate concentrations have lead to supraphysiological pyruvate levels that can affect the underlying metabolism and should be considered when interpreting results. With lactate serving as an important energy source for the heart and physiological lactate levels one to two orders of magnitude higher than for pyruvate, hyperpolarized lactate could potentially be used as an alternative to pyruvate for probing cardiac metabolism. In this study, hyperpolarized [1‐¹³C]lactate was used to acquire time‐resolved spectra from the healthy rat heart in vivo and to measure dichloroacetate (DCA)‐modulated changes in flux through pyruvate dehydrogenase (PDH). Both primary oxidation of lactate to pyruvate and subsequent conversion of pyruvate to alanine and bicarbonate could reliably be detected. Since DCA stimulates the activity of PDH through inhibition of PDH kinase, a more than 2.5‐fold increase in bicarbonate‐to‐substrate ratio was found after administration of DCA, similar to the effect when using [1‐¹³C]pyruvate as the substrate. Copyright © 2012 John Wiley & Sons, Ltd.     

Effect of triorthocresyl phosphate poisoning on intensity of incorporation of [2-14C]acetate into phospholipids and cholesterol of the guinea pig brain and spinal cord

A severe form of chronic triorthocresyl phosphate poisoning was induced in guinea pigs by a single intradermal injection of this compound and the intensity of incorporation of [2-¹⁴C]acetate into lipids of the spinal cord and brain stem was investigated in vivo. In the paralytic stage of the disease incorporation of the label into phospholipids and cholesterol was clearly reduced; inhibition of synthesis of these lipids was observed not only in the most vulnerable lumbosacral region of the spinal cord, but also in the brain stem, evidence of the systemic character of the disturbance of lipid metabolism in the CNS and of changes in the metabolism of the oligodendroglia.Department of Biochemistry, I. P. Pavlov First Leningrad Medical Institute. (Presented by Academician of the Academy of Medical Sciences of the USSR A. N. Klimov). Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 85, No. 4, pp. 427–429, April, 1978.     

Prostaglandin endoperoxides IX. Characterization of rabbit aorta contracting substance (RCS) from guinea pig lung and human platelets.

Material causing contraction of the isolated rabbit aorta (rabbit aorta contracting substance, RCS) was released from guinea pig lung following perfusion with arachidonic acid and from human blood platelets after addition of thrombin to induce aggregation. Prostaglandin endoperoxides (prostaglandins G2 and/or H2) were found both in the perfusate of guinea pig lung (1-3 ng/ml) and in the medium collected after platelet aggregation (13-37 ng/ml). The contractile response of the isolated rabbit aorta to the pure prostaglandins G2 and H2 was also determined. These data combined with the quantitative analyses of the endoperoxides released from the lungs and platelets showed that only a minor part of the rabbit aorta contracting activity was due to the prostaglandin endoperoxides. The major part of the activity consisted of very unstable material. The half life of this material was about 30 s at 37 degrees whereas at this temperature the prostaglandin endoperoxides had a half life of about 5 min.     

Topography of basal glucose utilization in rat thalamus and hypothalamus determined with (1-14C)-glucose

Summary High resolution autoradiography was used to study the basal pattern of glucose-utilization in the rat thalamus and hypothalamus. Rats were injected via chronic jugular catheter with (1-¹⁴C)-glucose and sacrificed 30 min later. The high resolution thaw-mount autoradiographic procedure, using 4 m frozen sections and nuclear emulsion, permited discrimination of regional variations in glucose-utilization that have not yet been described. Quantitative data were obtained by means of digital image analysis and computerized densitometry. In the thalamus, high activity was present in the anterodorsal, anteroventral, laterodorsal and reticular nuclei, while low activity was found in the mediodorsal and paraventricular nuclei. The autoradiographic pattern of glucose utilization in the thalamus corresponds largely to classical cytoarchitectonic subdivisions. In the hypothalamus, the median eminence, arcuate nucleus, and periventricular nucleus showed the lowest activity, whereas certain parts of the lateral hypothalamus appeared high. Very high activity was present in mammillary nuclei. The described detailed anatomical data of glucose-utilization may provide insights into the functional circuitry of thalamic and hypothalamic systems and serve as a baseline from which experimental manipulations can be assessed.Abbreviations ac anterior commisure - AD anterodorsal thalamic nucleus - AHy anterior hypothalamic area - APT anterior pretectal area - Arc arcuate hypothalamic nucleus - AV anteroventral thalamic nucleus - BST bed nucleus of the stria terminalis - ch choroid plexus - CM central medial thalamic nucleus - CL centrolateral thalamic nucleus - cp cerebral peduncle - Dk nucleus of Darkschewitsch - DLG dorsal lateral geniculate nucleus - EP entopeduncular nucleus - F nucleus of the fields of Forel - f fornix - fr fasciculus retroflexus - Gem gemini hypothalamic nucleus - HDB nucleus of the horizontal limb of the diagonal band - IAM interanteromedial thalamic nucleus - ic internal capsule - LD laterodorsal thalamic nucleus - LH lateral hypothalamic area - LHb lateral habenular nucleus - LM lateral mammillary nucleus - LP lateral posterior thalamic nucleus - MD mediodorsal thalamic nucleus - m central part - c central part - l lateral part - ME median eminence - MGD medial geniculate nucleus, dorsal part - MGV medial geniculate nucleus, ventral part - MHb medial habenular nucleus - ML medial mammillary nucleus, lateral part - ml medial lemniscus - MM medial mammillary nucleus, medial part - MP medial mammillary nucleus, posterior part - MPO medial preoptic area - MS medial septal nucleus - MT medial terminal nucleus of the accessory optic tract - mt mammillothalamic tract - mtg mammillotegmental tract - ox optic chiasm - pc posterior commissure - Pe periventricular hypothalamic nucleus - PF parafascicular thalamic nucleus - PMD premammillary nucleus, dorsal part - Po posterior thalamic nuclear group - PT paratenial thalamic nucleus - PV paraventricular thalamic nucleus - PVN paraventricular hypothalamic nucleus - RCh retrochiasmatic area - Rh rhomboid thalamic nucleus - Rt reticular thalamic nucleus - SCh suprachiasmatic nucleus - sm stria medullaris of the thalamus - SNC substantia nigra, compact part - SNR substantia nigra, reticular part - SPF subparafascicular thalamic nucleus - st stria terminalis - STH subthalamic nucleus - VL ventrolateral thalamic nucleus - VLG ventral lateral geniculate nucleus - m magnocellular part - p parvocellular part - VMH ventromedial hypothalamic nucleus - VPL ventral posterolateral thalamic nucleus - VPM ventral posteromedial thalamic nucleus - ZI zona incerta