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R G Vernon

Publications and source records attributed to R G Vernon.

At least 55 records · Page 3Linked to original sources
PubMed1996

Effect of lactation on insulin signal transduction in sheep adipose tissue and skeletal muscle.

The molecular basis of the insulin resistance of adipocytes and skeletal muscle during lactation has been investigated in sheep. The number of insulin receptors per adipocyte or per unit membrane protein for skeletal muscle is unchanged by lactation. The ability of insulin to stimulate autophosphorylation of its beta-subunit was enhanced in adipocytes but not in skeletal muscle during lactation. This increased autophosphorylation was due, at least in part, to enhanced tyrosine phosphorylation and was found when both solubilised, immunoprecipitated insulin receptors and intact adipocytes were incubated with insulin. The ability of the insulin receptor kinase to phosphorylate other proteins did not appear to be altered by lactation; this was shown with lectin-purified insulin receptors using the artificial substrate, polyglutamyl tyrosine, and in intact adipocytes. Lactation had no effect on the ability of insulin to activate two key downstream kinases, mitogen-activated protein kinase and phosphatidyl inositol-3-kinase in adipocytes. The study thus shows that the insulin resistance of lactation in sheep is due to changes downstream of the receptor in both adipocytes and skeletal muscle.

Adipose Tissue↗
PubMed1996

Chronic effects of somatotropin treatment on response of subcutaneous adipose tissue lipolysis to acutely acting factors in vivo and in vitro.

The basis of the chronic lipolytic effect of somatotropin on adipose tissue was investigated in sheep. Lipolytic rate was assessed in subcutaneous adipose tissue both in vivo, by microdialysis, and in vitro. Somatotropin treatment resulted in a small increase in basal (unstimulated) lipolysis and also in the maximum lipolytic rate observed in the presence of catecholamines both in vivo and in vitro. There was a small increase in the number of beta-adrenergic receptors but no change in the amount of the two isoforms of the stimulatory GTP-binding protein, Gs. Treatment with somatotropin decreased the response to antilipolytic agents such as the adenosine analog N6-phenylisopropyladenosine and prostaglandin E1. There was, however, no change in the number of adenosine receptors or amounts of the inhibitory GTP-binding proteins (Gi-1 plus Gi-2). Somatotropin also decreased prostaglandin E2 production by subcutaneous adipose tissue in vivo. Somatotropin treatment thus alters lipolytic regulation in sheep and this is characterized by changes in a number of proteins involved in this process.

Adipocytes↗
PubMed1995

Effects of lactation on the signal transduction systems regulating lipolysis in sheep subcutaneous and omental adipose tissue.

The effect of lactation on the regulation of lipolysis by beta- and alpha 2-adrenergic agents and by adenosine has been investigated. When changes in adipocyte mean cell volume (which decreases with lactation) are allowed for, lactation increased the maximum response both to beta-adrenergic agents and to the adenosine analogue N6-phenylisopropyladenosine, but had no apparent effect on the responsiveness of the alpha 2-adrenergic system in both subcutaneous and omental adipocytes. For subcutaneous adipocytes, there was no significant change in the number of beta-adrenergic or alpha 2-adrenergic receptors, but the amount of Gs and the maximum (forskolin-stimulated) adenylate cyclase activity were increased by lactation. In contrast, in omental adipocytes, the number of beta- (but not alpha 2-) adrenergic receptors and the amount of Gs were increased, whereas forskolin-stimulated adenylate cyclase activity was unchanged by lactation. In both types of adipocyte, cyclic AMP phosphodiesterase and total protein kinase A activities were unchanged. Lactation had no effect on the number of adenosine receptors but increased the amounts of the Gi isoforms expressed in both types of adipocyte. These various adaptations differ markedly in a number of respects from those described previously in the rat. Lactation, then, while having a similar overall effect on the response to beta-adrenergic agonists of adipocytes, achieves this by depot-specific mechanisms. In contrast, changes in response to adenosine appear to involve the same mechanism in the two depots investigated.

Adenylyl Cyclases↗
PubMed1995

Glucocorticoids regulate the secretion of a 21kDa-IGF-binding protein by sheep adipose tissue explants.

Using a solution phase assay we have demonstrated that sheep adipose tissue explants secrete insulin-like growth factor binding proteins (IGFBPs) when cultured in serum-free medium over a 24 h period. Further, we demonstrate that secretion of IGFBP(s) is inhibited (up to 50%) by incubation of the cultures in the presence of 10(-8) M dexamethasone. This inhibitory effect is overcome when insulin (10 ng/ml) and ovine growth hormone (100 ng/ml) are incubated together (but not separately) with glucocorticoid. Further characterisation of this IGF binding activity by high performance size exclusion chromatography and Western ligand blot analysis indicated that under our culture conditions sheep adipose tissue explants secrete one predominant 21 kDa IGFBP and it is this BP which is hormonally regulated as described above. We discuss our results in the context of endocrine/paracrine/autocrine control of adipose tissue metabolism and differentiation.

Adipose Tissue↗
PubMed1995

Glucocorticoids and insulin but not growth hormone modulate insulin binding to adipocyte membranes from sheep.

Mechanisms by which the glucocorticoid analogue dexamethasone and growth hormone modulate insulin action in sheep adipose tissue have been investigated. Maintenance of sheep adipose tissue in culture for 48 hr in the absence of exogenous hormones resulted in a decrease in insulin binding to adipocyte membranes; this was prevented by the inclusion of 10 nM dexamethasone during culture. Tissue culture for 48 hr with insulin itself decreased insulin binding to adipocyte membranes, whereas tissue culture with growth hormone had no effect on insulin binding. Neither dexamethasone nor growth hormone altered the ability of insulin to decrease insulin binding to its receptor. The study shows that the insulin-antagonistic effects of growth hormone on sheep adipose tissue metabolism are due to an effect subsequent to insulin binding to its receptor, whereas some of the effects of dexamethasone may be due to an increase in the insulin-binding capacity of membranes.

Adipocytes↗
PubMed1995

Effects of prolonged treatment of lactating goats with bovine somatotropin on aspects of adipose tissue and liver metabolism.

The effects of prolonged (22 weeks) treatment of lactating goats with bovine somatotropin on the metabolism of adipose tissue and liver has been investigated. Somatotropin treatment resulted in smaller adipocytes, decreased rate of fatty acid synthesis and decreased total acetyl-CoA carboxylase activity of adipocytes, but with no change in the proportion of this enzyme in the active state. The rate of acylglycerol glycerol synthesis from glucose of adipocytes tended to decrease as did total glucose utilization by the tissue. Glucose conversion to lactate was unchanged by somatotropin treatment but glucose conversion to other products was decreased. Maximum response of adipose tissue to insulin was unchanged but the sensitivity to insulin decreased on somatotropin treatment. Treatment with somatotropin had no effect on basal lipolysis and decreased maximum response to the beta-agonist isoproterenol, but this probably reflects the rate of isoproterenol-stimulated lipolysis varying with cell volume in adipocytes. No apparent change in response either to alpha 2-adrenergic agonists or to adenosine was apparent. The number of beta-adrenergic receptors was unchanged in adipocyte membranes but the number of alpha 2-adrenergic receptors increased. The rate of hepatic gluconeogenesis in vitro, the activity of key gluconeogenic enzymes and the modulation of the rate of gluconeogenesis by butyrate were unchanged except for the effect of this latter agent on gluconeogenesis from propionate. Hepatic ketogenic activity, as indicated by the activity of carnitine palmitoyl-CoA-transferase-1 and the concentrations of carnitine and acyl carnitines, was unchanged by treatment. Thus at the end of a prolonged period of treatment with somatotropin in lactating goats, lipid synthesis in adipose tissue is still decreased but no effects on liver lipid and carbohydrate metabolism were apparent.

Acetyl-CoA Carboxylase↗
PubMed1994

Growth hormone decreases the response to anti-lipolytic agonists and decreases the levels of Gi2 in rat adipocytes.

The effect of growth hormone (GH) in vivo on the Gi-mediated anti-lipolytic signalling system of rat adipocytes has been investigated. Lowering of serum GH levels, by treatment of rats with an antiserum (anti-rGH) specific for rat GH, increased the sensitivity of adipocytes to the anti-lipolytic agonists N6-phenylisopropyladenosine (PIA) and prostaglandin E1. This occurred in the absence of any change in PIA binding to adipocyte membranes. Immunoblot analysis of adipocyte membranes revealed that lowering of serum GH resulted in at least a 3-fold increase in the levels of alpha-subunit of Gi2, but had no effect on the alpha-subunits of Gi1 and Gi3 nor on the 42 and 45 kDa forms of the alpha-subunit of Gs. Replenishment of serum GH, by concurrent administration of ovine GH to rats, prevented all of these effects of anti-rGH. It is concluded that GH down-regulates the amount of Gi2 alpha-subunit in adipocyte membranes, resulting in a decrease in the sensitivity of the cells to anti-lipolytic agonists.

Adipose Tissue↗
PubMed1994

Increased neuropeptide Y concentrations in specific hypothalamic regions of lactating rats: possible relationship to hyperphagia and adaptive changes in energy balance.

Lactation is accompanied by hyperphagia and a reduction in brown adipose tissue (BAT) thermogenesis, which are unexplained. Neuropeptide Y (NPY) powerfully stimulates feeding and inhibits BAT thermogenesis when injected into the paraventricular nucleus and other specific regions of the rat hypothalamus. We have tested the hypothesis that hypothalamic NPY activity is increased in lactating rats. Lactating rats consumed over four times as much food as nonlactating controls (n = 10; p < 0.001). Final plasma insulin concentrations in lactating rats were lower than in controls (6.8 +/- 0.8 vs. 11.7 +/- 2.1 pmol/l; p < 0.05) although plasma glucose and corticosterone concentrations were comparable (p > 0.05). Lactating rats showed significantly higher NPY levels than controls in specific hypothalamic regions, namely the arcuate nucleus-median eminence complex (a 41% rise; p < 0.001), paraventricular nucleus (35%; p < 0.001), ventromedial nucleus (66%; p = 0.003), and dorsomedial nucleus (78%; p < 0.001). Other hypothalamic regions showed no significant differences between groups. Increased NPY concentrations in specific hypothalamic regions, particularly the arcuate nucleus where NPY is synthesized, suggest increased activity of the hypothalamic NPYergic system in lactation. Neuropeptide Y may mediate hyperphagia and reduced BAT thermogenesis in lactation. Hypoinsulinemia may be a stimulus to hypothalamic NPY in lactation, as has been postulated in other conditions of negative energy balance.

Adaptation, Physiological↗
PubMed1994

Growth hormone inhibition of lipogenesis in sheep adipose tissue: requirement for gene transcription and polyamines.

The chronic inhibitory effect of growth hormone (GH) on lipogenesis in sheep adipose tissue explants was investigated in an in vitro tissue culture system. In the absence of other hormones, GH caused a decrease in the rate of lipogenesis after 6 h of culture. In contrast, when lipogenesis was stimulated by the presence of insulin plus dexamethasone, GH again decreased lipogenesis but after a lag of at least 12 h. Actinomycin D, an inhibitor of gene transcription, prevented the effect of GH on lipogenesis in both the absence and presence of insulin plus dexamethasone. Actinomycin D added to tissue previously incubated for 6 h in the presence of GH alone prevented further decline in lipogenesis over the next 5 h, suggesting that transcription of a short-lived mediator protein is required for the GH effect to occur. An increase in ornithine decarboxylase activity was detected in explants exposed to GH, reaching a peak after 12 h incubation; this was prevented by actinomycin D. Methylglyoxal bis-(guanylhydrazone), an inhibitor of polyamine biosynthesis, partially alleviated the effect of GH on lipogenesis; this was reversed by addition of spermidine. However, spermidine did not reverse the effects of actinomycin D, implicating a short-lived protein in addition to ornithine decarboxylase in the action of GH. In the absence of other hormones GH had no effect on either the expressed (initial) or total activity of acetyl-CoA carboxylase, but GH prevented the increase in both expressed and total activities of the enzyme induced by insulin plus dexamethasone.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetyl-CoA Carboxylase↗
PubMed1993

Mechanisms involved in the adaptations of the adipocyte adrenergic signal-transduction system and their modulation by growth hormone during the lactation cycle in the rat.

The mechanisms responsible for the diminished lipolytic response of adipocytes to catecholamines after litter removal from lactating rats and their modulation by growth hormone have been investigated. Lactation, litter removal and growth-hormone treatment did not alter the ability of noradrenaline to activate protein kinase A (A-kinase), showing that the defect in signal transduction in rats after litter removal is after A-kinase. Litter removal had no effect on hormone-sensitive lipase activity itself, but the proportion of the lipase associated with the fat droplet was decreased; growth-hormone treatment increased hormone-sensitive lipase activity and the proportion associated with the fat droplet. In addition, a number of other adaptations in the beta-adrenergic signal-transduction system occur during the lactation cycle and in response to growth hormone treatment, including changes in receptor number, adenylate cyclase activity and cyclic AMP phosphodiesterase activity, but a defect in the ability of hormone-sensitive lipase to associate with the lipid droplet appears to be the major reason for the diminished response to catecholamines on litter removal.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1993

Endocrine control of sheep adipose tissue fatty acid synthesis: depot specific differences in response to lactation.

The effects of lactation and insulin, growth hormone and dexamethasone (a glucocorticoid analogue) have been assessed on the rate of fatty acid synthesis in adipose tissue from omental (abdominal), subcutaneous and popliteal (intermuscular) depots of sheep. Adipocyte mean cell volume was greatest in omental tissue but the rate of fatty acid synthesis was similar in omental and subcutaneous adipose tissue in non-lactating ewes. Insulin increased the rate of fatty acid synthesis in tissue from all three depots and this was antagonised by growth hormone. The effects of growth hormone were less in omental adipose tissue from non-lactating sheep than in the other two depots. Lactation decreased the rate of fatty acid synthesis in all three depots, but to a lesser extent in omental than the other depots. Insulin resistance was apparent in subcutaneous and popliteal tissues from lactating ewes but not in omental tissue. Omental adipose tissue, thus differs in several aspects from the two carcass depots. Differences in response to hormones in omental adipose tissue were apparent in young sheep before the onset of fattening when omental adipocytes are similar in size to subcutaneous adipocytes.

Adipose Tissue↗