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Biomedical subjects

R G Vernon

Publications and source records attributed to R G Vernon.

At least 109 records · Page 6Linked to original sources

Catecholamine activation of pyruvate dehydrogenase in white adipose tissue of the rat in vivo.

Intraperitoneal injections of noradrenaline or adrenaline into rats increased the proportion of pyruvate dehydrogenase in the active state in white adipose tissue; this effect of catecholamines was also apparent in streptozotocin-diabetic rats, showing that it was not due to an increase in serum insulin concentration. The catecholamine-induced increase in pyruvate dehydrogenase of white adipose tissue in vivo was completely blocked by prior injection of either the beta-antagonist propranolol or the alpha 1-antagonist prazosin. Cervical dislocation of conscious rats increased pyruvate dehydrogenase activity of white adipose tissue, which was prevented by prior injection of propranolol. Adrenaline (30 nM) activated pyruvate dehydrogenase in white adipocytes in vitro; the maximum effect of adrenaline required activation of both alpha 1- and beta-receptors. The results show that catecholamines activate pyruvate dehydrogenase of white adipose tissue both in vivo and in vitro and that this effect is mediated by a combination of alpha 1- and beta-adrenergic receptors.

Adipose Tissue↗

Relationships between plasma hormone concentrations, udder development and the production of early mammary secretions in twin-bearing ewes on different planes of nutrition.

Ewes carrying twin fetuses were maintained during late pregnancy on a uniformly high plane (well fed), a uniformly low plane (underfed) or a low plane rising to a high plane (refed) of nutrition. The maternal plasma concentrations of hormones concerned with udder development, colostrum production and milk secretion were measured in samples obtained during the last 32 d before and the first 18 h after birth. Udder weights were derived from their linear dimensions, the yields of mammary secretions by hand milking during the first 18 h after birth and the transition from colostrum to milk was indicated by changes in the concentrations of lactose, lipid and immunoglobulin G. Underfeeding reduced prenatal udder development and colostrum accumulation and delayed the post-natal transition to milk secretion. Refeeding previously underfed ewes to a high plane during the last 5 d before birth had no effect on udder growth, but it did return the secretory functions of udder tissue to the levels observed in well-fed ewes. Nutritional effects on the plasma concentrations of insulin, placental lactogen, prolactin, cortisol and oestradiol-17 beta were small or absent. The relative changes in the plasma concentrations of growth hormone and insulin were such that the growth hormone: insulin ratio increased markedly during the last 11 d before birth in the underfed and refed ewes but not in the well-fed ewes. These differences in the growth hormone: insulin ratio were associated with greater increases in udder growth rate in the underfed and refed ewes than in the well-fed ewes. The plasma concentrations of progesterone decreased before birth in all ewes, but the decrease was delayed by underfeeding and refeeding rapidly overcame this effect. The slower progesterone withdrawal in the underfed ewes was associated with a delay in lactogenesis. It is concluded that the nutritionally induced changes in the growth hormone: insulin ratio and in the progesterone concentrations were the most likely endocrine determinants of the observed differences in the rates of mammogenesis and lactogenesis, respectively, but possible independent effects of substrate supply to the udder remain to be clarified.

Animals↗

Effects of long-term thrice-daily milking on mammary enzyme activity, cell population and milk yield in the goat.

In two separate experiments, lactating goats were milked unilaterally thrice daily instead of twice daily for periods of 13 and 37 wk, starting at 2 to 5 wk after parturition. The other gland was milked twice daily throughout. In both experiments thrice-daily milking increased milk yield significantly. In the first experiment, after 37 wk the amounts of RNA and DNA, rate of cell proliferation and activities of several enzymes per cell were greater in the thrice-milked gland (P less than .05). In the second experiment, after 9 or 10 d of thrice-daily milking the activities of several key mammary enzymes per cell measured in biopsy samples had increased in the thrice-milked but not the twice-milked gland. After 13 wk of thrice-daily milking, the DNA content of the glands and the activity per cell of the key enzymes was the same in both glands, showing that the synthetic capacity of the gland was being used more effectively in the treated gland. These results indicate that several mechanisms contributed to the increased milk yield induced by thrice-daily milking.

Animals↗

Enzymes of glucose and fatty acid metabolism of liver, kidney, skeletal muscle, adipose tissue and mammary gland of lactating and non-lactating sheep.

The effect of peak lactation on the activities of a number of enzymes of glucose and lipid metabolism of perirenal and subcutaneous adipose tissue, skeletal muscle, liver, kidney cortex and mammary parenchyma of sheep are described. Enzymes studied included hexokinase (glucose utilization), pyruvate carboxylase (gluconeogenesis), pyruvate dehydrogenase (glucose oxidation and production of acetyl CoA for fatty acid synthesis), acetyl CoA carboxylase (fatty acid synthesis) and glycerol-3-phosphate acyltransferase (fatty acid esterification). Major changes that were found include a decrease in activities of enzymes of fatty acid synthesis and esterification in adipose tissues, decreased activity of pyruvate dehydrogenase in muscle and adipose tissues and increased pyruvate carboxylase; there was no change in activities of enzyme of fatty acid esterification in liver. Activities of hexokinase, acetyl CoA carboxylase and glycerol-3-phosphate acyltransferase have been estimated per tissue; this shows the quantitative importance of limiting glucose utilization by muscle and of suppression of fatty acid synthesis in adipose tissue for efficient partitioning of nutrients for milk production.

Adipose Tissue↗

Employee testing raises workplace privacy issues.

With increasing frequency, employers are considering mandatory screening for substance abuse and AIDS. These tests are focusing attention on an area of growing concern for hospitals--employees' right to privacy in the workplace--and prompting trustees to define an institutional philosophy for their hospital.

Acquired Immunodeficiency Syndrome↗

Lipolysis in rat adipocytes during recovery from lactation. Response to noradrenaline and adenosine.

The replenishment of lipid reserves of adipocytes following the removal of litters from lactating rats is associated with a 3-fold decrease in both the response of lipolysis to noradrenaline and the maximum rate of lipolysis (measured in the presence of noradrenaline plus adenosine deaminase); these adaptations do not appear to result from the changes in serum prolactin and insulin concentrations that occur on litter removal.

Adenosine↗

Adipose tissue metabolism in sheep: response to season and its modulation by reproductive state.

Seasonal changes in subcutaneous adipose tissue metabolism and serum metabolite and hormone concentrations are described in virgin ewes fed a fixed amount of a cereal mixture plus hay ad libitum. Body weight, adipocyte mean cell volume, the rates of fatty acid and acylglycerol glycerol synthesis, and lipoprotein lipase activity increased from October to May and then decreased over the following five months. These changes are probably due to an increase in voluntary food intake leading to increased availability of acetate for fatty acid synthesis and also a probable rise in serum insulin concentration. Seasonal changes in adipose tissue metabolism in sheep are modulated by pregnancy and lactation, possibly mediated in part by changes in the serum insulin: growth hormone ratio. Although seasonal changes in adipose tissue metabolism are paralleled by changes in serum prolactin concentration, prolactin probably does not have a direct effect on adipose tissue metabolism.

Adipose Tissue↗

Enzymes of adenosine metabolism of sheep adipose tissue: changes in activity with season, pregnancy and lactation.

Activities of enzymes involved in the synthesis and degradation of adenosine have been measured in samples of adipose tissue from unmated sheep at various times of the year between January and October and from pregnant and lactating sheep. 5'-Nucleotidase activity increased during the spring in unmated sheep but this increase was suppressed in lactating sheep. Neither adenosine kinase nor adenosine deaminase activities varied significantly between January and October in unmated sheep. Lactation resulted in a rise in adenosine deaminase activity and a small decrease in adenosine kinase activity. Pregnancy had no obvious effect on the activities of any of the three enzymes noted above. Changes in adipocyte mean cell volume and number per g tissue and the concentrations of DNA and protein of the tissue are also described. Results are discussed in relation to changes in the capacity for lipid synthesis and mobilization which occur in response to season, pregnancy and lactation in sheep.

5'-Nucleotidase↗

Acetyl-CoA carboxylase of sheep adipose tissue: problems of the assay and adaptation during fetal development.

The rate of fatty acid synthesis of perirenal adipose tissue of fetal lambs decreased by 90% during the last month of gestation. There was also a 90% decrease in the activity of fatty acid synthetase during this period, but the activity of this enzyme exceeded lipogenic flux by a factor of 10. The activity of acetyl CoA carboxylase in the active state (initial activity) was very similar to the lipogenic flux in adipose tissue from lambs at 120 d of gestation; although activity decreased towards term, the decline was insufficient to account for the fall in rate of fatty acid synthesis. The study also shows that assay of acetyl CoA carboxylase in the active state of ovine adipose tissue and of caprine mammary gland requires the presence of citrate, thus differing from that for rat adipose tissue. Evidence that pyruvate carboxylase can interfere in the assay of acetyl CoA carboxylase also is presented.

Acetyl-CoA Carboxylase↗

Regulation of lipolysis during pregnancy and lactation in sheep. Response to noradrenaline and adenosine.

The effects of pregnancy and lactation on lipolysis in sheep adipose tissue in vitro were investigated. Neither pregnancy nor lactation altered the basal rate of lipolysis. The rate of noradrenaline-stimulated lipolysis was directly proportional to adipocyte mean cell volume. Lactation, but not pregnancy, increased the response to noradrenaline, but had no effect on the ED50 of noradrenaline. The adenosine analogue N6-phenylisopropyladenosine decreased the rate of lipolysis in the presence of noradrenaline; the effect was greater with adipose tissue from lactating than from control, unmated, sheep. Results are discussed in relation to the need of sheep to mobilize lipid during early lactation to support milk production.

Adenosine↗

Insulin processing and action in adipocytes: evidence for generation of insulin-containing vesicles by leupeptin and monensin.

Incubation of adipocytes with 125I-insulin plus leupeptin or monensin, but not chloroquine, resulted in the appearance of a novel peak of 125I-insulin (modal density about 1.20 g/ml) on density gradient centrifugation; the appearance of the peak depended on the presence of specific insulin receptors on the cell surface. The fractions comprising this peak contained vesicles, probably originating from the Golgi apparatus, and dit not appear to be contaminated with lysosomes, mitochondria or plasma membrane. Entrapment of insulin in these vesicles per se did not prevent the activation of glucose transport, acetyl-CoA carboxylase or pyruvate dehydrogenase by insulin.

Acetyl-CoA Carboxylase↗

Adaptations of adipose tissue metabolism and number of insulin receptors in pregnant sheep.

The endocrine control of adipose tissue metabolism during pregnancy in sheep has been investigated. The number of insulin receptors of sheep adipocytes was increased during pregnancy. There was no apparent change in the concentration of serum insulin during pregnancy in sheep while the rise in serum progesterone concentration was smaller and more gradual than in rats. Net lipid deposition in adipocytes occurred during the first 55 days of pregnancy, probably due primarily to increased lipoprotein lipase activity. Net deposition of lipid had ceased by mid-pregnancy while by 125 days of pregnancy, the rate of fatty acid synthesis in adipose tissue was decreased and the serum fatty acid concentration had risen, suggesting the onset of net lipid mobilization in the tissue. Results are compared with those from other studies with rats; it would appear that different mechanisms regulate lipid deposition during pregnancy in sheep and rats.

Adaptation, Physiological↗

Fatty acid synthesis from amino acids in sheep adipose tissue.

The rates of incorporation of 14C from 14C labelled acetate, glucose, alanine, leucine, isoleucine and valine into fatty acids has been measured in perirenal adipose tissue from foetal lambs and 8-month-old sheep, and into both fatty acids and acylglycerol glycerol in adipose tissue from 3-year-old sheep and 220-240 g female rats. Rates of incorporation of 14C from amino acids into fatty acids were much lower in adipose tissue from sheep (at all three ages) than from rats, whereas rates of incorporation of 14C into acylglycerol glycerol were either greater in sheep adipose tissue or the same as in rat adipose tissue. The rate of incorporation of 14C from amino acids into fatty acids decreased in the order leucine greater than alanine greater than isoleucine greater than valine in adipose tissue from rats and foetal lambs, and in the order leucine greater than alanine = isoleucine greater than valine in adipose tissue from 8-month- and 3-year-old sheep. Amino acids make a very small contribution to fatty acid synthesis in adipose tissue from sheep at all stages of development examined while fatty acids are a minor product of amino acid metabolism in sheep adipose tissue. The study provides further evidence for an important role for ATP-citrate lyase in restricting the utilization of acetyl-CoA generated in the mitochondria for fatty acid synthesis.

Acetates↗

Insulin binding and action on bovine adipocytes.

The present study was undertaken to determine whether bovine adipocytes could bind and respond to insulin. Adipose tissue from young bulls showed little response to physiological and higher concentrations of insulin over a 3-h incubation. In contrast, insulin did stimulate glucose uptake during prolonged incubations and also increased the activity of pyruvate kinase; in each case, half-maximum stimulation was observed with concentrations of about 0.5 ng/ml. Specific binding of [125I] iodoinsulin to bovine adipocytes was observed; the binding capacity was greater than that of young female rats determined under the same conditions. Bovine adipocytes internalized insulin. Incubation of bovine adipocytes with insulin resulted in a concentration-dependent loss of insulin receptors from the adipocyte surface. In summary, bovine adipocytes possess the capacity to both bind and respond to insulin; these findings are discussed in relation to a recent report to the contrary.

Adipose Tissue↗

Adenosine and the control of lipolysis in rat adipocytes during pregnancy and lactation.

The rate of noradrenaline-stimulated lipolysis is lower in fat-cells from lactating than from pregnant rats; this difference is eliminated by the addition of adenosine deaminase [Aitchison, Clegg & Vernon (1982) Biochem. J. 202, 243-247]. The activity of 5'-nucleotidase, and hence the capacity of the cells to synthesize adenosine, was the same in fat-cells and also stromal cells of adipose tissue from pregnant, lactating and male rats. The response and sensitivity of fat-cells to the anti-lipolytic effects of adenosine were measured by incubating cells in the presence of noradrenaline, adenosine deaminase (to remove endogenous adenosine) and various concentrations of the adenosine analogue N6-phenylisopropyladenosine (PIA). PIA caused a greater inhibition of the rate of noradrenaline-stimulated lipolysis in adipocytes from lactating than from pregnant rats. The concentration of PIA required to inhibit by 50% the rate of noradrenaline-stimulated lipolysis fell from over 100 nM for fat-cells from pregnant rats to 30 nM for fat-cells from lactating rats. The decreased rate of noradrenaline-stimulated lipolysis during lactation was not due to the smaller mean cell volume of adipocytes during this state.

5'-Nucleotidase↗

Adipose tissue metabolism during early pregnancy in the rat: temporal relationships of changes in the metabolic activity, number of insulin receptors, and serum hormone concentrations.

The temporal relationships between changes in rates of fatty acid and acylglycerol glycerol synthesis; the activity of lipoprotein lipase of parametrial adipocytes and their capacity to bind insulin; and the serum concentrations of insulin, progesterone, prolactin, and total lactogenic activity have been examined in rats during the first 15 days of pregnancy. The rate of fatty acid and acylglycerol synthesis showed a transient increase at Days 9 and 12 of pregnancy, whereas there was no change in the activity of lipoprotein lipase activity except for a fall between Days 12 and 15 of pregnancy. The capacity of adipocytes to bind insulin was increased by Day 6 of pregnancy and remained elevated until at least Day 15; no changes in the affinity for insulin were observed. Serum progesterone, insulin, and total lactogenic activity were elevated by Days 3, 9, and 12 of pregnancy, respectively. The results show that progesterone but not placental lactogen could be responsible for the rise in the insulin-binding capacity of rat adipocytes during pregnancy, whereas the fall in lipogenic capacity at about Day 12 of pregnancy coincides with the rise in serum placental lactogen.

Adipose Tissue↗

Glucose metabolism and its regulation in pieces of perirenal adipose tissue from foetal lambs.

1. The following were measured in pieces of perirenal adipose tissue obtained from foetal lambs at about 120 days of gestation or within 3 days of term, and 9-month-old sheep: the rates of synthesis from glucose of fatty acids, acylglycerol glycerol, pyruvate and lactate; the rate of glucose oxidation to CO2 and the proportions contributed by the pentose phosphate cycle, pyruvate dehydrogenase and the tricarboxylic acid cycle; the activities of hexokinase, glucose 6-phosphate dehydrogenase, phosphofructokinase, pyruvate kinase and pyruvate dehydrogenase. 2. The total rate of glucose utilization was lower in pieces of adipose tissue from near-term lambs than 120-day foetal lambs and the pattern of glucose metabolism differed, with, for example, a much smaller proportion of glucose carbon being used for fatty acid synthesis, whereas a greater proportion of glucose oxidation occurred via the tricarboxylic acid cycle in the near-term lambs. In general, these differences in glucose metabolism were not associated with differences in the activities of the various enzymes listed above. 3. The rates of glucose utilization per fat-cell by 120-day foetal lambs and 9-month-old sheep were very similar but, again, the proportions metabolized to the various products differed. In particular, there was a smaller proportion of glucose oxidized via the pentose phosphate cycle and a greater proportion oxidized via pyruvate dehydrogenase and the tricarboxylic acid cycle in adipose tissue from foetal lambs. These differences were matched by a lower activity of glucose 6-phosphate dehydrogenase and a higher pyruvate dehydrogenase activity in fat-cells from the foetal lambs.

Adipose Tissue↗

Control of fatty acid synthesis in lactation.

Lactation results not only in an increased rate of fatty acid synthesis in the mammary gland but also in a decreased rate of fatty acid synthesis in adipose tissue and, in the rat at least, an increased rate of hepatic fatty acid synthesis. Progesterone (during pregnancy), prolactin and (in ruminants) GH are implicated in the regulation of the reciprocal changes in fatty acid synthesis in mammary gland and adipose tissue. Progesterone and prolactin, at least, appear to influence the rate of fatty acid synthesis by modulating the insulin-binding capacities of the tissues, but it is clear that steps in the mechanism of action of insulin subsequent to its binding to the receptor are also changed in adipose tissue during lactation.

Adipose Tissue↗