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E Vara

Publications and source records attributed to E Vara.

At least 55 records · Page 3Linked to original sources
PubMed1993

Effect of sepsis-related cytokines on lipid synthesis by isolated human hepatocytes.

OBJECTIVE: To investigate the effect of tumour necrosis factor-alpha (TNF-alpha) and other sepsis related cytokines on the synthesis of several lipid fractions by human hepatocytes. DESIGN: Laboratory study. SETTING: University departments of surgery and biochemistry. MATERIAL: Livers from eight donors of other organs. MAIN OUTCOME MEASURES: Effect of TNF-alpha, interleukin-1 (IL-1), and interleukin-6 (IL-6) on the synthesis of triacylglycerol and phospholipids by freshly isolated human hepatocytes. RESULTS: All three cytokines, particularly TNF-alpha, inhibited the incorporation of D-glucose uniformly labelled with 14C (D-(U-14C) glucose) into phosphatidylcholine. The incorporation of D-(U-14C) glucose into triacylglycerol and free fatty acids was significantly stimulated by TNF-alpha and IL-1, but not by IL-6. When palmitate uniformly labelled with 14C was used as the radiolabelled precursor, TNF-alpha stimulated the synthesis of both triacylglycerol and phosphatidylcholine, neither of which was affected by IL-1 or IL-6. CONCLUSION: Changes that are induced by cytokines in lipid synthesis by hepatocytes can contribute to the impairment of lipid metabolism seen in septic patients. TNF-alpha seemed to have more effect than the other two cytokines.

Adult↗
PubMed1993

Tumour necrosis factor-alpha inhibits synthesis of surfactant by isolated human type II pneumocytes.

OBJECTIVE: To investigate the effect of tumour necrosis factor-alpha (TNF-alpha) on the synthesis of surfactant by human type II pneumocytes. DESIGN: Laboratory study. SETTING: University departments of surgery and biochemistry. MATERIAL: Segments of right lower lobe of lungs from nine donors of other organs, and from tumour-free portions of 10 lungs excised from patients with lung cancer. MAIN OUTCOME MEASURES: Effect of TNF-alpha on the incorporation of D-glucose and palmitate, both of which had been uniformly labelled with 14C (D-(U-14C) glucose and (U-14C) palmitate), into various phospholipid fractions by pneumocytes isolated from both healthy lungs and those from patients with lung cancer. RESULTS: TNF-alpha decreased the incorporation of both D-(U-14C) glucose and (U-14C) palmitate into phospholipid fractions, particularly phosphatidylcholine, in both healthy lung tissue and that from patients with lung cancer. The degree of inhibition was less in the group from patients with lung cancer because the basal value was lower. CONCLUSION: TNF-alpha may contribute to the pathophysiology of the adult respiratory distress syndrome by inhibiting the synthesis of surfactant. The results suggest the possibility that TNF-alpha may be produced locally in the presence of lung cancer resulting in chronic paracrine or systemic exposure of pneumocytes to low concentrations of the cytokine.

Adult↗
PubMed1991

Does cyclic guanosine monophosphate mediate noradrenaline-induced inhibition of islet insulin secretion stimulated by glucose and palmitate?

Noradrenaline inhibits in rat islets the stimulation of insulin secretion induced by glucose and its potentiation by palmitate, but the signalling system responsible remains unknown. We have tested the hypothesis that noradrenaline-induced inhibition is mediated by an elevation of cyclic GMP (cGMP) levels. The analogue 8-Br-cGMP decreases dose-dependently the potentiation by palmitate of glucose-induced insulin secretion, whereas it only slightly affects the proper effect of glucose. Similarly, it abolishes palmitate acceleration of glucose-induced 45Ca2+ uptake without modifying the sugar effect. Finally, 8-Br-cGMP completely inhibits the stimulation of the lipid synthesis de novo induced by palmitate, but not that caused by glucose alone. On the other hand, noradrenaline increases dose-dependently islet cGMP content, with alpha 2-adrenergic specificity. As noradrenaline-induced elevation of cGMP is sensitive to pertussis toxin, it probably results from alpha 2-adrenoceptor activation of islet guanylate cyclase through a guanine nucleotide regulatory protein. It is concluded that the elevated cGMP levels mediate noradrenaline inhibition of lipid synthesis de novo, and hence of acceleration by palmitate of 45Ca2+ uptake and insulin secretion in the presence of glucose.

Animals↗
PubMed1991

Different secretory response of pancreatic isolated lobules and dissociated acini from hypothyroid rats to exogen TRH.

This paper analyses the effect of hypothyroidism on pancreatic TRH and somatostatin concentrations, as well as the action of exogen TRH on pancreatic amylase secretion from isolated lobules and dissociated acini of both healthy and hypothyroid rats. In the hypothyroid group, pancreatic TRH and somatostatin increased. In the pancreatic lobules of untreated animals, bethanechol produced stimulatory action that was inhibited by TRH. On the other hand, lobules from hypothyroid rats did not respond to bethanechol stimulation. Acini amylase secretion after bethanechol stimulation was similar in both groups, although hypothyroid animals were more sensitive to the inhibitory effect of TRH. These findings suggest the existence of a factor blocking the amylase secretion in pancreatic lobules. This agent, probably TRH, could be eliminated in the experimental model of dissociated acini.

Amylases↗
PubMed1991

Effects of calcium channel blockers on insulin secretion and 45Ca(2+)-uptake of rat islets stimulated by glucose or K(+)-depolarization.

Two calcium channel antagonists, verapamil and nifedipine, have been used to explore the dependence of secretion on voltage-gated influx of calcium. Both antagonists were able to suppress the secretory response to K(+)-depolarization as well as the stimulation of 45Ca(2+)-uptake. However, they inhibited only partially the stimulation of both secretion and 45Ca(2+)-uptake. However, they inhibited only partially the stimulation of both secretion and 45Ca(2+)-uptake induced by glucose, alone or with palmitate. The stimulation of 45Ca(2+)-uptake by K(+)-depolarization, unlike that induced by glucose, was not sensitive to norepinephrine, starvation or fatty acid oxidation inhibitors. Therefore, it is suggested that glucose either modifies the properties of the voltage-dependent calcium channel and/or accelerates the exchange of a particular intracellular pool of calcium.

Animals↗
PubMed1990

Insulin, glucagon, somatostatin, and thyrotropin-releasing hormone content and secretion by perifused fetal rat islets during culture.

In the neonatal period of the rat, pancreatic thyrotropin-releasing hormone content decreases and the sensitivity of insulin secretion to glucose increases. In adult rat islets, TRH inhibits glucose-induced insulin release. The aim of this study was to investigate whether a high TRH content and release can be part of the explanation for the functional immaturity of neonatal islets. For that purpose, we have measured the tissue content and the secretion of immunoreactive insulin, glucagon, somatostatin and TRH in islets from 21.5-day-old rat fetuses cultured for up to one week. Insulin, glucagon and somatostatin content increased during one week of culture in the presence of 11.1 mmol/l glucose. The TRH content decreased during culture, but did not equal adult values. Insulin, glucagon and somatostatin responses to glucose were present after one week of culture. Glucose had no effect on TRH release in cultured fetal islets, but inhibited TRH release in adult islets. We conclude that glucose can stimulate insulin secretion without inhibiting TRH release, but that a decrease in islet TRH content and a sensitization of TRH secretion to glucose may be important in the full maturation of fetal pancreatic islets.

Animals↗
PubMed1990

Trifluoperazine reproduces in rat islets the effects of calcium omission on insulin secretion and de novo lipid synthesis, without affecting 45Ca2(+)-uptake.

Calmodulin is thought to mediate at least some of the effects produced by the elevation of cytosolic calcium in response to a B-cell secretagogue. Trifluoperazine, an inhibitor of calcium-calmodulin interaction, has been used to test, comparatively with calcium-omission, whether the changes of lipid metabolism accompanying the stimulation of insulin release by glucose and palmitate are dependent on activation by the calcium binding protein. Low doses of trifluoperazine (1 and 5 mumol/l) reproduced quantitatively and qualitatively the effects of calcium omission on both insulin secretion and de novo lipid synthesis, without altering islet 45Ca2(+)-uptake. The apparent dependence on calcium-calmodulin of the "de novo" synthesis of neutral lipids, but not of acidic phospholipids, might reflect a possible regulation of islet phosphatidate phosphohydrolase by calcium.

Animals↗
PubMed1989

Norepinephrine inhibits islet lipid metabolism, 45Ca2+ uptake, and insulin secretion.

We have previously shown that palmitate potentiates, in isolated islets, glucose-induced stimulation of insulin release, "de novo" lipid synthesis, and 45Ca2+ turnover in a correlative manner. Norepinephrine, a known inhibitor of the secretory response, has now been used to further investigate the relationships among the three phenomena. The amine decreased insulin secretion dose dependently in response to glucose and palmitate with alpha 2-adrenergic specificity. It also reduced similarly the oxidation of 1 mmol/l [U-14C]palmitate as well as the incorporation of 20 mmol/l D-[U-14C]glucose into islet phospholipids and neutral lipids through an alpha 2-adrenergic mechanism. These results indirectly suggest that alpha 2-adrenoceptor stimulation inhibits in islets both palmitate oxidation and esterification through an inactivation of long-chain acyl-CoA synthetase and other enzymes of glycerolipid synthesis. Islet uptake of 45Ca2+ was also decreased by norepinephrine with a similar sensitivity to that shown by insulin release and de novo lipid synthesis. Therefore, it is suggested that alpha 2-adrenoceptor-mediated reduction of the potentiation by palmitate of the secretory response to glucose depends on the inhibition of fatty acid metabolism and the resulting impairment of de novo lipid synthesis and 45Ca2+ turnover.

Animals↗
PubMed1988

Palmitate dependence of insulin secretion, "de novo" phospholipid synthesis and 45Ca2+-turnover in glucose stimulated rat islets.

Palmitate ability to modify D-[U-14C]glucose incorporation into different lipids ("de novo" synthesis), as well as sugar-stimulation of insulin release and 45Ca2+-fluxes, was investigated in islets of fed and 48-h starved rats. The fatty-acid induced dose-dependent, correlative increments of insulin secretion, 45Ca2+-influx and the "de novo" synthesis of each phospholipid fraction analysed at 20 mmol/l (but not 3 mmol/l) glucose. Omission of calcium reduced drastically (p less than 0.001) insulin release and the "de novo" synthesis of neutral glycerolipids, leaving unaltered that of acidic phospholipids (phosphatidate and phosphoinositides). The increased synthesis of the latter is therefore not the consequence of stimulated secretion. It could initiate or contribute to maintain an increased turnover of islet phosphoinositides, thus generating some mediators of the calcium signalling system (inositol phosphates). Starvation led to a drastic reduction (p less than 0.001) of both insulin secretion, "de novo" synthesis of each lipid fraction, and 45Ca2+-influx in response to glucose and palmitate. The presence of a fatty-acid oxidation inhibitor (2-bromostearate or 2-tetradecylglycidate) prevented the effect of starvation on 45Ca2+-influx, as it has been shown to do on insulin secretion and palmitate incorporation into islet lipids. It is finally suggested that palmitate might amplify the insulin secretory response of islets to glucose, through the stimulation of the "de novo" synthesis of phosphoinositides and the subsequent generation of inositol phosphates, which would contribute to accelerated calcium turnover.

Animals↗
PubMed1988

Islet secretion of immunoreactive thyrotropin-releasing hormone and the 'paracrine-like' effects of its exogenous administration.

In order to know more about the secretory pattern of islet TRH in response to glucose and its possible physiological relevance, the release of this hormone as well as that of insulin, glucagon, and somatostatin was radioimmunologically measured. Whereas the secretion of immunoreactive insulin and somatostatin by incubated rat islets is known to be dose-dependently stimulated by glucose, that of glucagon and TRH was inhibited by glucose. Similarly, palmitate dose-dependently inhibited islet glucagon and TRH release. Exogenous TRH exerted strong and dose-dependent effects on islet secretion of the other hormones at the same concentration range at which its hypophysiotropic effects are produced (10(-10) to 10(-8) mol/l). It inhibited the insulin response to glucose and blocked that of glucagon, whereas it enhanced glucose-induced stimulation of somatostatin. These results are suggestive of a possible paracrine inhibitory role of islet TRH, either directly exerted on the secretion of insulin and glucagon or partially mediated through the stimulation of somatostatin release.

Animals↗
PubMed1986

Glucose stimulation of insulin secretion in islets of fed and starved rats and its dependence on lipid metabolism.

The influence of a physiologic range of palmitate concentrations (0, 0.25, 0.5, and 1.0 mmol/L) on glucose ability to modify insulin secretion, (U-14C) palmitate oxidation, and (U-14C) glucose incorporation into lipids has been studied in islets isolated from either fed or 48-hour starved rats. Palmitate potentiated the insulin response of fed islets to glucose in a particular dose-related manner. Glucose stimulated secretion was accompanied by a decreased palmitate oxidation and an increased (U-14C) glucose incorporation into di-, tri-acylglycerols, and predominantly into phospholipids. These metabolic parameters showed also a positive dependence on palmitate concentration. Starvation increased islet capacity to oxidize palmitate, rendered it insensitive to glucose inhibition, and inhibited both (U-14C) glucose incorporation into all lipid fractions and sugar induced insulin release. The stimulation of islet lipid synthesis by glucose seems to be limited by the exogenous supply of fatty acids and their rate of oxidation. As judged from (U-14C) glucose incorporation data, the rate of phospholipid biosynthesis showed a significant and positive correlation with insulin secretion. This metabolic pathway might provide islet cells with some lipid intermediates (diacylglycerol and/or specific phospholipids) that have been considered as possible mediators of the calcium messenger system.

Animals↗