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B Leighton

Publications and source records attributed to B Leighton.

83 records · Page 5Linked to original sources
PubMed1987

Maximum activities of some key enzymes of glycolysis, glutaminolysis, Krebs cycle and fatty acid utilization in bovine pulmonary endothelial cells.

Despite the importance of endothelial cells little is known about their metabolic fuel requirements. To provide some information in this area, the maximum catalytic activities of key enzymes of important metabolic pathways have been measured in bovine pulmonary endothelial cells. The results suggest that both glucose and glutamine are important fuels for these cells: in addition, the oxidation of fatty acids may also be of quantitative significance. The activity of glutaminase in these cells was about 20-fold higher than that in lymphocyte, a cell which exhibits high rates of glutaminolysis. It is suggested that a high rate of glutamine metabolism by endothelial cells is important not only for energy provision but also for provision of nitrogen for biosynthetic purposes including production of local messengers.

Animals↗
PubMed1987

Effects of dexamethasone treatment on insulin-stimulated rates of glycolysis and glycogen synthesis in isolated incubated skeletal muscles of the rat.

1. Rats were treated with dexamethasone for 4 days before measurement of the rates of lactate formation [which is an index of hexose transport; see Challiss, Lozeman, Leighton & Newsholme (1986) Biochem. J. 233, 377-381] and glycogen synthesis in response to various concentrations of insulin in isolated incubated soleus and extensor digitorum longus muscle preparations. 2. The concentration of insulin required to stimulate these processes half-maximally in soleus and extensor digitorum longus muscles isolated from control rats was about 100 muunits/ml. 3. Dexamethasone increases the concentration of insulin required to stimulate glycolysis half-maximally in soleus and extensor digitorum longus preparations to 250 and 300 muunits/ml respectively. The respective insulin concentrations necessary to stimulate glycogen synthesis half-maximally were about 430 and 370 muunits/ml for soleus and extensor digitorum longus muscle preparations isolated from steroid-treated rats. 5. Dexamethasone treatment did not change the amount of insulin bound to soleus muscle.

Animals↗
PubMed1987

Effects of prolonged elevation of plasma adrenaline concentration in vivo on insulin-sensitivity in soleus muscle of the rat.

1. Prolonged elevation of the plasma adrenaline concentration was produced in rats by implantation of adrenaline-releasing retard-tablets. With this technique, a hyperadrenalinaemic state is maintained for at least 5 days. 2. At 6 h after implantation of the retard-tablet it was found that plasma glucose and fatty acid concentrations increased and insulin concentration decreased compared with values obtained from placebo-tablet-implanted rats. Administration of a subcutaneous glucose load demonstrated an impaired glucose tolerance in vivo, and incubation of soleus muscle strips from 6 h-hyperadrenalinaemic rats in vitro demonstrated a decreased sensitivity of the rates of glycolysis and glucose transport to insulin. 3. The sensitivities of the rates of glycolysis, glucose transport and glycogen synthesis to insulin were determined for the incubated soleus muscle preparation isolated from animals after 48 h, 72 h and 120 h duration of hyperadrenalinaemia. At 48 h after retard-tablet implantation, the sensitivity of the processes of glucose transport and glycolysis was decreased; at 72 h, the insulin-sensitivities of the rates of glycolysis and glucose transport in skeletal muscle were similar to those determined for control animals; at 120 h, however, the sensitivities of the processes of glucose transport and glycolysis were both statistically significantly increased. In contrast, no changes in the sensitivity of the process of glycogen synthesis were observed at any of the time intervals studied. 4. The possible biochemical basis for the observed changes in skeletal-muscle insulin-sensitivity with prolonged hyperadrenalinaemia is discussed.

3-O-Methylglucose↗
PubMed1987

Effects of chronic administration of vanadate to the rat on the sensitivity of glycolysis and glycogen synthesis in skeletal muscle to insulin.

Male Wistar rats were given sodium orthovanadate in their drinking water for at least 14 days. This treatment increased the hypoglycaemic effect of intravenously administered insulin and increased the sensitivity of isolated soleus muscle strips to insulin with respect to both glycolytic and glycogen synthetic rates. This effect of chronic vanadate administration was shown not to be a consequence of a change in the insulin binding characteristics of soleus muscle. It is suggested that these changes may be brought about by the interaction of vanadate with insulin-mediated alterations in tyrosine kinase/phosphotyrosyl phosphatase activities.

Animals↗
PubMed1987

Effects of dipyridamole on adenosine concentration, insulin sensitivity and glucose utilisation in soleus muscle of the rat.

Adenosine has been shown to modulate the sensitivity of skeletal muscle to insulin (Budohoski et al. 1984). In an attempt to further characterize the modulatory action of adenosine on insulin sensitivity in skeletal muscle we have investigated the effect of the nucleoside transport inhibitor dipyridamole in isolated incubated soleus muscle strips. At a concentration of 50 microM, dipyridamole increased the concentration of adenosine in the soleus muscle by 36% and in the incubation medium by 32%. At this concentration of dipyridamole, the basal rates (in the presence of 1 microunit of insulin/ml) of lactate formation, 2-deoxy [2,6-3H]glucose phosphorylation and glucose oxidation were decreased by 48%, 43% and 47% respectively, whilst the rate of glycogen synthesis was unaffected. Insulin-stimulated rates (in the presence of 10,000 microunits of insulin/ml) of lactate formation, 2-deoxy [2,6-3H] glucose phosphorylation, glycogen synthesis and glucose oxidation were decreased by 70%, 30%, 26% and 20% respectively in the presence of 50 microM dipyridamole. Although 50 microM dipyridamole was required to exert a significant effect on medium and soleus muscle adenosine concentrations, statistically significant effects on glycolytic rate were observed at concentrations as low as 2 microM dipyridamole. It is concluded that the results are not consistent with dipyridamole exerting an effect on skeletal muscle carbohydrate metabolism solely through elevation of the intracellular or interstitial adenosine concentration, but strongly suggest that dipyridamole inhibits glucose transport and/or phosphorylation in skeletal muscle.

Adenosine↗
PubMed1987

The effect of dehydroepiandrosterone acetate on liver peroxisomal enzyme activities of male and female rats.

The present study is a follow-up to the report that dehydroepiandrosterone (DHEA) acetate treatment in rats stimulated metabolic heat production and suppressed serum triglycerides, adiposity and weight gain without affecting food intake. Activities of peroxisomal fatty acyl-coenzyme (CoA) oxidase and catalase as well as mitochondrial citrate synthase were assayed in liver tissue of 24 young adult male and female Wistar rats fed a nonpurified diet containing 0.6% DHEA (6 g/kg) for 6 wk. DHEA-treated animals gained less weight but had heavier liver weights than did the controls. Hepatic activity of fatty acyl-CoA oxidase of the experimental male and female animal was 1058 and 946% higher, respectively, than that of the controls. For catalase activity, only the female groups were different (30%). Activity of citrate synthase was not affected by DHEA. These data support the hypothesis that the inhibitory effect of DHEA on energy storage as fat is mediated, at least in part, by increased beta-oxidation of fatty acids in peroxisomes. The peroxisomal beta-oxidation pathway is uncoupled from oxidative phosphorylation; electrons are transferred directly to molecular O2 because of cycling of NAD/NADH resulting in the expenditure of chemical energy as heat.

Acyl-CoA Oxidase↗
PubMed1986

Effects of the beta-adrenoceptor agonist isoprenaline on insulin-sensitivity in soleus muscle of the rat.

The interactions between a beta-adrenoceptor agonist (isoprenaline) and insulin on rates of hexose transport, glucose phosphorylation, glycogen synthesis and glycogenolysis were investigated in the incubated stripped soleus-muscle preparation of the rat. In the presence of 1 microM-isoprenaline, insulin was less effective in stimulating glucose phosphorylation and glycogen synthesis. The stimulation of glycogenolysis by isoprenaline was only slightly decreased even at high (10000 microunits/ml) concentrations of insulin. Insulin-stimulated phosphorylation of 2-deoxyglucose was decreased by isoprenaline. It is suggested that this decrease in the rate of glucose phosphorylation is caused by the observed elevated concentration of glucose 6-phosphate, which inhibits hexokinase activity. This conclusion is supported by the fact that isoprenaline had no effect on the stimulation of 3-O-methylglucose transport by insulin.

3-O-Methylglucose↗
PubMed1985

The effect of prostaglandins E1, E2 and F2 alpha and indomethacin on the sensitivity of glycolysis and glycogen synthesis to insulin in stripped soleus muscles of the rat.

Prostaglandins E1 and E2 increased the sensitivity of glycolysis to insulin in the isolated stripped soleus muscle of the rat, but prostaglandin F2 alpha had no effect. Indomethacin, which inhibits prostaglandin formation, markedly decreased the sensitivity of glycolysis to insulin. These findings suggest that prostaglandins of the E series increase the sensitivity of muscle glycolysis to insulin in vivo.

Animals↗
PubMed1983

The pathway of ketogenesis in rumen epithelium of the sheep.

A method for the fractionation of sheep rumen epithelium with limited mitochondrial breakage is described. The distributions of the enzymes of the 3-hydroxy-3-methylglutaryl-CoA pathway of ketogenesis indicate that this process is exclusively mitochondrial. Enzyme activities are sufficient to account for the ketogenic rates found in vivo. The failure of (-)-hydroxycitrate to block ketogenic flux supports this view. 3-Hydroxybutyrate dehydrogenase activity is largely associated with particulate material in the mitochondrial fraction. ATP citrate lyase activity was found, with appreciable acetoacetyl-CoA thiolase and 3-hydroxy-3-methylglutaryl-CoA synthase in the cytoplasmic fraction.

Animals↗