Evolution of myocardial glycolysis in perinatal rats]

Glycolysis was assessed in the Langendorff perfused rat heart during the perinatal period. Glucose uptake, lactate production, 14C-glucose incorporation into glycogen, tissue content content of glycogen, lactate and high energy phosphates were measured in the foetus of 21.5 days post co?tum and in the newborn of 1 and 7 days post partum. Glycogen synthesis and anaerobic glycolysis were found to be more active in the foetal heart and to decrease during the first neonatal week.     

Development of noradrenaline uptake in the human foetal heart

Summary The development of NA-uptake mechanisms in the human foetal heart start at the same time as the adrenergic terminals were visible. The highest³H-NA values in the human foetal heart were only 25–30% of those found in the mouse heart.Acknowledgment. The technical assistance of Miss Marjo Martonen is gratefully acknowledged. This investigation was supported by a grant from the National Research Council for Medical Science, Finland.     

Kinetics of insulin secretion in response to glucose by isolated islands of Langerhans from the fetal rat]

Isolated islets of Langerhans from 21.5 day-old foetal Rats were studied in a perifusion system in vitro. The overall dynamics of insulin release by the foetal islets in response to glucose 13.9 mM is biphasic and qualitatively similar to that obtained with islets of adult Rats. The magnitude of the initial phase of insulin secretion is similar for the foetal and adult islets. The second phase is fourfold higher in the adult than in the foetus. The response of foetal islets occurs, 45 to 60 sec. after the increase of glucose concentration in the medium and a maximum insulin release for the first phase is obtained with a lag period of 2 min. The difference between foetal and adult islets is essentially quantitative.     

Glykogenbildung nach Thymektomie

Summary (1) No differences were found in the glycogen contents in liver, heart, and various other muscles between thymectomized and normal rats.(2) There are likewise no differences in glycogen synthesis in the diaphragm in the presence of glucose, alone and with insulin, between thymectomized and normal rats.(3) The weight of adrenal glands, absolute as well as in relation to the body-weight, shows no difference too between thymectomized and normal rats.     

Dial variations in the levels of blood glucose and hepatopancreatic glycogen in the slug,Laevicaulis alte (Ferussac 1821)

Summary InLaevicaulis alte maximal blood glucose level at 00.00 h alternates with minimal level at 12.00 h of the day, while hepatopancreatic glycogen showed an opposite trend. Variations in blood glucose levels are inversely proportional to the corresponding variations in hepatopancreatic glycogen content, while blood glucose level shoots up to a maximum, hepatopancreatic glycogen declines to a minimum and vice versa.Acknowledgment. The authors thank Prof. K.S. Swami for providing facilities. The financial assistance rendered by ICMR (DCR), UGC (VJ) and CSIR (KS), New Delhi, India is gratefully acknowledged.     

Mapping and quantification of biomolecules in tumor biopsies using bioluminescence

Quantitative bioluminescence and single-photon imaging have been applied for mapping concentration distributions of metabolites, such as adenosine triphosphate (ATP), glucose and lactate, in biopsies of cervical cancers in patients. Biopsies were taken before a conventional radiation treatment, and a number of clinically relevant data, such as local tumor control, patient survival, metastatic spread and so forth, were documented. There was no correlation between staging or grading and any of the metabolic parameters measured. Local correlations between ATP, glucose and lactate on a pixel-to-pixel basis were generally positive, with respective Spearman's correlation coefficients less in patients without clinically documented metastasis compared with those with metastatic spread. Lactate concentrations were significantly higher and scattered over a wider range in tumors with metastatic spread in comparison to malignancies in patients without metastasis. Thus, high local lactate levels of 20 mole/g appear to be associated with a high risk of metastasis, at least in human cervical tumors.     

Effect of high lipid diet on circadian rhythms of tissue glycogen

Summary The well defined circadian rhythms of glycogen content in heart, diaphragm and liver of the rat are drastically altered by a high lipid diet as shown by changes in amplitude, phase and tissue glycogen levels. If sampling times had been restricted to certain hours of the day the profound effect of the high fat diet on tissue glycogen would not have been apparent.Supported by USPHS grants HL 16041-03 and HL 07094-03.     

Possible involvement of indolamines in the glycogenic effect of the convulsant methionine sulfoximine in rat brain.

The aim of the present investigation was to look for the mechanisms causing disturbances in carbohydrate metabolism during the action of the epileptogenic agent methionine sulfoximine. The levels of glucose, glycogen, and indolamines were measured in seven different regions of rat brain. Methionine sulfoximine induced a decrease in serotonin level which was roughly dose-dependent. There were no obvious changes in tryptophan and 5-hydroxyindoleacetic levels in any area. Methionine sulfoximine induced the known increase in glucose and glycogen levels. The direct precursor of serotonin. 5-hydroxytryptophan, and benserazide (a decarboxylase inhibitor) were then injected into rats in association with methionine sulfoximine. In this case, methionine sulfoximine failed to induce seizures. Moreover, the serotonin level was unchanged and the carbohydrate content did not significantly increase. There was only a rise in 5-hydroxyindoleacetic acid level. This work shows a striking parallelism between serotonin decrease and glycogen increase.     

Possible involvement of indolamines in the glycogenic effect of the convulsant methionine sulfoximine in rat brain

Summary The aim of the present investigation was to look for the mechanisms causing disturbances in carbohydrate metabolism during the action of the epileptogenic agent methionine sulfoximine The levels of glucose, glycogen, and indolamines were measured in seven different regions of rat brain. Methionine sulfoximine induced a decrease in serotonin level which was roughly dose-dependent. There were no obvious, changes in tryptophan and 5-hydroxyindoleacetic levels in any area. Methionine sulfoximine induced the known increase in glucose and glycogen levels. The direct precursor of serotonin, 5-hydroxytryptophan, and benserazide (a decarboxylase inhibitor) were then injected into rats in association with methionine sulfoximine. In this case, methionine sulfoximine failed to induce seizures. Moreover, the serotonin level was unchanged and the carbohydrate content did not significantly increase. There was only a rise in 5-hydroxyindoleacetic acid level. This work shows a striking parallelism between serotonin decrease and glycogen increase.     

Myocardial function and energy metabolism in carnitine-deficient rats

Carnitine is essential for mitochondrial metabolism of long-chain fatty acids and thus for myocardial energy production. Accordingly, carnitine deficiency can be associated with cardiomyopathy. To better understand this disease, we determined myocardial function and energy metabolism in a rat model of carnitine deficiency. Carnitine deficiency was induced by a 3- or 6-week diet containing N-trimethyl-hydrazine-3-propionate, reducing cardiac and plasma carnitine by 70-85%. Myocardial function was investigated in isolated isovolumic heart preparations. Carnitine-deficient hearts showed left ventricular systolic dysfunction, reduced contractile reserve, and a blunted frequency-force relationship independently of the substrate used (glucose or palmitate). After glycogen depletion, palmitate could not sustain myocardial function. Histology and activities of carnitine palmitoyl transferase, citrate synthase, and cytochrome c oxidase were unaltered. Thus, as little as 3-6 weeks of systemic carnitine deficiency can lead to abnormalities in myocardial function. These abnormalities are masked by endogenous glycogen and are not accompanied by structural alterations of the myocardium or by altered activities of important mitochondrial enzymes.     

Changes in plasma levels of metabolites during long-term fasting in the goose]

In fed geese, plasma levels of glucose and alanine were 1.9 g.l-1 and 560 mumol.l-1, respectively. During a long fast (40 days), plasma glucose and alanine were maintained at a high level (1.5-1.8 g.l-1 and 370-540 mumol.l-1, respectively). Plasma level of acetoacetate was very low (40 mumol.l-1); by contrast, plasma level of beta hydroxybutyrate reached very high values (20 mmol.l-1) after about 20 days of fasting, then it decreased. Plasma levels of lactate and pyruvate decreased along the course of the fast, from 2 500 to 2 000 mumol.l-1 and 220 to 170 mumol.l-1, respectively.     

Depletion of cellular glycogen during the early logarithmic growth phase of human fibroblasts

Summary Human diploid fibroblasts deplete 50% of their cellular glycogen by day 4 after subcultivation in 100 mg% glucose medium. The glycogen content increases again as the cells approach confluency. Growth of cells in low glucose medium results in rapid glycogen depletion and indicates that stored glycogen has a limited potential as an energy source.Supported in part by a grant from the Frank G. Bressler Fund.     

The effects of salicylate and aspirin on the activity of phosphorylase a in perfused hearts of rats

Summary Sodium salicylate and aspirin are known to have a glycogenolytic effect as judged by either the glycogen level or lactate production in perfused hearts of rats. In this work it was possible to demonstrate that phosphorylase a level was increased in the hearts subjected to the action of these drugs.     

Post-transcriptional gene silencing of ribosomal protein S6 kinase 1 restores insulin action in leucine-treated skeletal muscle

Excessive nutrients, especially amino acids, impair insulin action on glucose metabolism in skeletal muscle. We tested the hypothesis that the branched-chain amino acid leucine reduces acute insulin action in primary myotubes via a negative feedback mechanism involving ribosomal protein S6 kinase 1 (S6K1). The effect of S6K1 on glucose metabolism was determined by applying RNA interference (siRNA). Leucine (5 mM) reduced glucose uptake and incorporation to glycogen by 13% and 22%, respectively, compared to the scramble siRNA-transfected control at the basal level. Leucine also reduced insulin-stimulated Akt phosphorylation, glucose uptake and glucose incorporation to glycogen (39%, 39% and 37%, respectively), and this reduction was restored after S6K1 silencing. Depletion of S6K1 enhanced basal glucose utilization and protected against the development of impaired insulin action, in response to excessive leucine. In conclusion, S6K1 plays an important role in the regulation of insulin action on glucose metabolism in skeletal muscle. Received 22 December 2008; received after revision 19 February 2009; accepted 23 February 2009     

Einbau von H3-d-glucose während der Oogenese beiApis mellifica L.

Summary The incorporation of tritiated glucose into the ovary of honey bee queens was studied by autoradiography. During the last stages of oogenesis, the synthesis of respectable amounts of glycogen was found in the reticuloplasm of the developing eggs. The follicle epithelium and also the nurse cells only appeared more lightly and transitory labelled at medium stages. An hypothesis was established concerning an antagonism of protein and polysaccharide formation in the cytoplasm corresponding to the rather late occurrence of glycogen in insect oogenesis.     

Aldose metabolism in developing human fetal brain and liver

Aldose reductase, sorbitol dehydrogenase, and glucose-6-phosphate dehydrogenase enzyme activities were studied in human foetal brain and liver at different periods of gestation. Aldose reductase activity in liver disappears after 16 weeks of gestation whereas sorbitol dehydrogenase keeps on increasing in liver as well as in brain. In utero, some glucose metabolism may be mediated through an active sorbitol pathway in human fetuses.     

Effect of organophosphate pesticide Sumithion (Fenitrothion) on some aspects of carbohydrate metabolism in a freshwater fish, Sarotherodon (Tilapia) mossambicus (Peters)

A lethal (Lc50/48 h - 6 mg/l) concentration of the organophosphate (OP) pesticide Sumithion increased blood glucose levels and phosphorylase activity, but hepatic glycogen registered a fall which indicated that the observed hyperglycemia was due to breakdown of hepatic glycogen.     

Effect of various stressors on the levels of lipid peroxide,antioxidants and Na+, K+-ATPase actrivity in rat brain

The level of malondialdehyde (MDA), an index of lipid peroxidation, and the antioxidants superoxide dismutase (SOD) and glutathione (GSH), as well as the activity of Na⁺, K⁺-ATPase, were assessed in whole rat brain after immobilization, anemic hypoxia (NaNO₂) and 72 h starvation. The effect of these stressors on plasma glucose and corticosterone levels was also observed. Hypoxia and starvation stimulated the lipidj peroxide formation in braini as indicated by an increase in the level of MDA, being higher after starvation than hypoxia. Brain SOD activity was also increased in response to hypoxia and starvation while GSH content was only diminished ini hypoxia. However, neither MDA nor antioxidants were affected by immobilization. On the other hand, the activity of brain Na⁺, K⁺-ATPase was significantly increased by immobilization and hypoxia but decreased in starvation. A similar pattern of change was also observed in plasma glucose and corticosterone levels in response to these stressors. These results elucidate differences in the biochemical response of animals towards various types of stress, with increased lipid peroxide formation in hypoxia and starvation.     

Über die Wirkung blutzuckersenkender Sulfonylharnstoffe auf das isolierte Rattenzwerchfell

Summary The action of blood sugar depressing sulfonylureas on glucose and oxygen uptake, as well as on glycogen content and formation of C¹⁴O₂ from uniformly labelled C¹⁴-glucose was investigated in rat hemidiaphragms incubated in phosphate buffer. The following results were obtained: (1) Tolbutamide and Carbutamide increased the glucose uptake. (2) Tolbutamide decreased the glycogen-content. (3) Oxygen uptake as well as formation of C¹⁴O₂ were increased by Tolbutamide. (4) The action of Tolbutamide and insuline was equal with respect to glucose uptake but different as regarding the glycogen content, oxygen uptake and CO₂-formation.It is concluded that sulfonylureas increase glucose oxidation in the rat hemidiaphragm probably without increasing insulin sensitivity. To our knowledge this mechanism of action has hitherto not been described.     

Serotonin is localized in endothelial cells of coronary arteries and released during hypoxia: A possible new mechanism for hypoxia-induced vasodilatation of the rat heart

Summary In this report we demonstrate the immunocytochemical localization of serotonin in endothelial cells of rat coronary vessels and a significant increase in the release of serotonin into the perfusate of Langendorff rat heart preparations during hypoxia. It is suggested that serotonin, localized in endothelial cells, is released during hypoxia and could provide part of a pathophysiological mechanism for vasodilatation to protect the heart from damage due to hypoxia.This research was supported by the British Heart Foundation and the excellent technical assistance of Jon Bokor is gratefully acknowledged.