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Biomedical subjects

E Shafrir

Publications and source records attributed to E Shafrir.

At least 109 records · Page 6Linked to original sources
PubMed1978

Placental enzymes of glycolysis, gluconeogenesis and lipogenesis in the diabetic rat and in starvation. Comparison with maternal and foetal liver.

The activity of several regulatory enzymes representing the pathways of glycolysis, gluconeogenesis, NADPH generation and lipogenesis was measured in rat placenta maternal and foetal livers on the 20th day of gestation. Streptozotocin diabetes, induced on the 12th day of gestation, or 48 h of fasting did not induce adaptive changes in the activity of placental enzymes while producing a typical insulin deficiency pattern in maternal liver. Foetal liver enzyme activities were unaffected by fasting and in diabetes showed changes suggestive of foetal hyperinsulinaemia. A small increase was observed in the activity of placental pyruvate kinase and a small decrease in that of PEP carboxylase in diabetic and in glucocorticoid-treated rats; these changes were reciprocal to those in the maternal liver and were attributed to hyperglycaemia, as was the increase in placental glycogen. Lack of response to insulin deficiency and to other endocrine alterations indicates that placenta is not sensitive to stimuli which induce adaptive alterations in hepatic enzymes. The only consistent change found in placental enzyme activities was a decrease associated with gestational age.

Animals↗
PubMed1977

Evidence for an accelerated adaptation to starvation in chronic uremia.

During a 72-hr period of starvation plasma levels of glucose and immunoreactive insulin fell to a greater extent, and alanine, free fatty acid, and glycerol concentrations were higher in fasted chronically uremic rats than in nonuremic controls. These changes, in conjunction with a significant increase in the uremic group's activity of phosphoenolypyruvate-carboxykinase, the rate-limiting enzyme in hepatic gluconeogenesis, after only 12 hr of fasting suggest that alterations in glucose metabolism in uremia may contribute to an exaggeration and acceleration of the metabolic consequences of starvation.

Adaptation, Physiological↗
PubMed1976

Interaction of glucocorticoid hormones with rat skeletal muscle: catabolic effects and hormone binding.

The mechanism of action of glucocorticoid hormones on rat skeletal muscle was studied by following their effect on muscle weight, free amino acid content, activity of amino acid-metabolizing enzymes, and binding to cytoplasmic receptor proteins. A significant reduction of gastrocnemius muscle and body weight occurred following administration of cortisol, triamcinolone diacetate, and triamcinolone acetonide to adrenalectomized rats. Treatment with triamcinolone diacetate also reduced the level of several free amino acids and enhanced the activity of a myofibrillar protease in skeletal muscle. The hormone had, however, no effect on the activity of various enzymes involved in amino acid catabolism in muscle. In nephrosis, another condition of muscle wasting, the level of several muscle amino acids were also reduced to a lesser extent. Cortisol and triamcinolone acetonide, both of which induce muscle wasting, were found to bind to two distinct cytoplasmic proteins in muscle. Binding of the labeled hormones was followed at 0 C and could be observed in presence of a 1000-fold excess of the catabolically inactive steroid epicortisol. Binding of 3H-triamcinolone acetonide. In vitro competition experiments further suggest a correlation between steroid binding to the 3H-dexamethasone or 3H-triamcinolone acetonide site and their potency to induce muscle catabolism. It is concluded that skeletal muscle is a direct target organ for glucocorticoids, and that muscle responsiveness involves binding of the active hormones to cytoplasmic receptor sites.

Amino Acids↗
PubMed1976

The role of hypovolemic stress in the production of fat embolism in rabbits. 1. Morphologic alterations of the lungs.

In rabbits, an experimental model of fat embolism was produced that simulates the course of events in the clinical situation. Small doses of fat-cell suspension (0.075 ml/kg of body weight), prepared by collagenase treatment of homologous adipose tissue, were injected intravenously. Concomitantly, hypovolemia was produced in two animal groups by either withdrawing 20 percent of the estimated blood volume or by application of a hind-limb ischemic tourniquet for 90 minutes. The presence of pathoanatomic characteristics typical of fat embolism was evaluated by recording lung/body weights, macroscopic appearance, and semiquantitative microscopic estimation in the lungs of edema, hemorrhage, atelectasis, intravascular coagulation, and leukocytic thrombi. Mean indices of lung/body weight were higher in all animals receiving injections of fat-cell suspension, as compared to controls. The score for microscopic generalized pulmonary damage was significantly higher in rabbits exposed to both fat-cell injections and hypovolemia than in controls or after fat-cell injections alone. It is concluded that hypovolemia enhances the development of fat embolism in rabbits subjected to small doses of fat-cell suspension.

Animals↗
PubMed1976

The role of hypovolemic stress in the production of fat embolism in rabbits. 2. Changes in arterial blood gas levels and static compliance.

The purpose of this study was to assess the possible role of hypovolemia as a factor in the production of impaired pulmonary function in pulmonary fat embolizaiton. Iv vivo static lung compliance was measured by inflating the lungs with known volumes of air and recording the transpulmonary pressure, monitoring intraesophageal pressure as an index of intrapleural pressure. Arterial blood was drawn from the central artery of the ear. Embolization was produced by the intravenous injection of homologous fat cells either as the sole experimental procedure or in conjunction with hypovolemic shock. Two types of shock were studied. In one, 20 percent of the blood volume was removed, producing hypovolemia associated with hemodilution, and in the other a tourniquet was applied to induce hypovolemia and hemoconcentration. The results indicate that embolization is associated with significantly greater impairment of pulmonary function if it develops on a background of shock than if it occurs in an otherwise healthy animal. These pathophysiologic findings parallel the results of a morphologic study.

Adipose Tissue↗
PubMed1976

Activity of placental enzymes of carbohydrate and lipid metabolism in normal, toxemic and small-for-date pregnancies.

The specific activity of placental enzymes with a regulatory function in the pathways of glycolysis, gluconeogenesis, NADPH generation and fatty acid synthesis decrease during gestation in the rat. Similar decreases occur in the activity of enzymes of the human placenta when compared between early gestation and term, with the exception of the activity of enzymes related to gluconeogenesis which tend to increase as gestation advances. In term placentas from pregnancies complicated by preeclamptic toxemia, enzyme activities were significantly lower than those in placentas from normal pregnancies, irrespective of whether the baby was of normal weight or small-for-date. This indicates an accelerated decline in placental metabolic function in toxemia. In contrast, in placentas from nontoxemic pregnancies with small-for-date babies the enzyme activities were significantly higher than those in normal term placentas. It is suggested that the decrease in placental enzyme activity, which is associated with placental growth during the course of normal gestation, is retarded in nontoxemic pregnancies with small-for-date babies, apparently due to the arrested aging of the placenta.

Animals↗
PubMed1975

Modulation of the activity of insulin-dependent enzymes of lipogenesis by glucocorticoids.

Administration of triamcinolone or dexamethasone to rats led to a prompt, marked and persistent rise in liver acetyl-CoA carboxylase activity. The activity of fatty acid synthetase increased to a lesser extent and after a more prolonged glucocorticoid treatment, whereas the changes in that of NADP-malate dehydrogenase and ATP-citrate lyase were not appreciable. The overall channeling of [1-14-C]acetyl-CoA to fatty acids was enhanced. The triamcinolone effect on acetyl-CoA carboxylase activity appeared to be dependent on the coincident hyperinsulinemia since it was not obtained in alloxan-diabetic rats, whereas the alanine-aminotransferase-inducing effect of this hormone was additive to that of insulin deficiency. In adipose tissue triamcinolone treatment caused a reduction in the activity of all lipogenesis enzymes and blunted their response to insulin administration. The antagonism of glucocorticoids toward insulin, selectively modulating the responses of the insulin-sensitive enzymes in liver and adipose tissue is discussed. The rise in hepatic lipogenic capacity, through the retention of the ability of insulin to induce acetyl-CoA carboxylase, may be physiologically important in restraining the ketogenesis from acetyl-CoA despite the increased fat utilization during glucocorticoid excess.

ATP Citrate (pro-S)-Lyase↗
PubMed1975

Effect of chorionic gonadotropin, triamcinolone, progesterone and estrogen on enzymes of placenta and liver in rats.

The activity of several enzymes of regulatory importance for the pathways of glycolysis, gluconeogenesis and lipogenesis was investigated in the placenta and liver of pregnant rats and in the liver of non-pregnant female rats. The rats received daily hormonal treatments on Days 15 to 17 of pregnancy and enzyme activities were measured on Day 18. Chorionic gonadotropin induced minor changes in enzyme activity, apart from a decrease in the activity of hepatic enzymes of lipogenesis in non-pregnant rats. Triamcinolone induced a marked increase in enzymes of gluconeogenesis and a decrease in the activity of pyruvate kinase in the liver of pregnant and non-pregnant rats; in contrast, inverse changes in activity, these enzymes were observed in the placenta. This response in the placenta was considered to arise not from direct hormone effect, but from the accompanying hyperglycemia and hyperinsulinemia. Triamcinolone also increased the activity of hepatic acetyl-CoA carboxylase in pregnant and non-pregnant rats, whereas it reduced the activity of this enzyme in the placenta. Estrogen produced changes similar to those of triamcinolone in the liver and placenta, except that it depressed the activity of acetyl-CoA carboxylase in both tissues. Progesterone had little effect on placental and hepatic enzymes. In general, the changes induced by these hormones in the placenta affected fewer enzymes than in the liver, were less extensive in magnitude and not necessarily in the same direction as in the liver. This indicates that the regulatory placental enzymes are subject to specific control mechanisms not necessarily influenced by direct hormone action.

Acetyl-CoA Carboxylase↗
PubMed1975

Enzymes of glucose and fatty acid metabolism in early and term human placenta.

The activity of enzymes involved in glycolysis, gluconeogenesis, and lipoenesis in early and term human placenta was determined. A high activity of pyruvate kinase was found, indicating high glycolytic potential. The activity of this enzyme tended to decrease with gestation. The presence of phosphoenolpyruvate carboxylase activity was detected, suggesting the possibility of gluconeogenesis in the placenta. Very low activity of enzymes involved in fatty acid synthesis was found, whereas the activity of the pentose shunt pathway enzymes, glucose-6-phosphogluconate dehydrogenases, was relatively high. This suggested a role of this pathway in the synthesis of lipids other than fatty acids in the placenta. The activities of enzymes in the human placenta and their changes during gestation where compared to previous observations on enzymes in rat placenta.

ATP Citrate (pro-S)-Lyase↗