Metabolic Conditions (metabolic + condition)

Distribution by Scientific Domains

Selected Abstracts

Intermediate metabolism in normal pregnancy and in gestational diabetes

G. Di Cianni
Abstract Complex though integrated hormonal and metabolic changes characterize pregnancy. In the face of progressive decline in insulin action, glucose homeostasis is maintained through a compensatory increase in insulin secretion. This switches energy production from carbohydrates to lipids, making glucose readily available to the fetus. This precise and entangled hormonal and metabolic condition can, however, be disrupted and diabetic hyperglycemia can develop (gestational diabetes). The increase in plasma glucose level is believed to confer significant risk of complications to both the mother and the fetus and the newborn. Moreover, exposition of fetal tissues to the diabetic maternal environment can translate into an increased risk for development of diabetes and/or the metabolic syndrome in the adult life. In women with previous gestational diabetes, the risk of developing type 2 diabetes is greatly enhanced, to the point that GDM represents an early stage in the natural history of type 2 diabetes. In these women, accurate follow-up and prevention strategies are needed to reduce the subsequent development of overt diabetes. This paper will review current knowledge on the modifications occurring in normal pregnancy, while outlining the mechanisms. In this paper, we will review the changes of intermediary metabolism occurring during pregnancy. In particular, we will outline the mechanisms responsible for gestational diabetes; the link between these alterations and associated maternal and neonatal morbidity will be examined. Copyright © 2003 John Wiley & Sons, Ltd. [source]

Metabolic responses in ischemic myocardium after inhalation of carbon monoxide

Background: To clarify the mechanisms of carbon monoxide (CO) tissue-protective effects, we studied energy metabolism in an animal model of acute coronary occlusion and pre-treatment with CO. Methods: In anesthetized pigs, a coronary snare and microdialysis probes were placed. CO (carboxyhemoglobin 5%) was inhaled for 200 min in test animals, followed by 40 min of coronary occlusion. Microdialysate was analyzed for lactate and glucose, and myocardial tissue samples were analyzed for adenosine tri-phosphate, adenosine di-phosphate, and adenosine mono-phosphate. Results: Lactate during coronary occlusion was approximately half as high in CO pre-treated animals and glucose levels decreased to a much lesser degree during ischemia. Energy charge was no different between groups. Conclusions: CO in the low-doses tested in this model results in a more favorable energy metabolic condition in that glycolysis is decreased in spite of maintained energy charge. Further work is warranted to clarify the possible mechanistic role of energy metabolism for CO protection. [source]

NADH supplementation decreases pinacidil-primed IK(ATP) in ventricular cardiomyocytes by increasing intracellular ATP

Brigitte Pelzmann
The aim of this study was to investigate the effect of nicotinamide-adenine dinucleotide (NADH) supplementation on the metabolic condition of isolated guinea-pig ventricular cardiomyocytes. The pinacidil-primed ATP-dependent potassium current IK(ATP) was used as an indicator of subsarcolemmal ATP concentration and intracellular adenine nucleotide contents were measured. Membrane currents were studied using the patch-clamp technique in the whole-cell recording mode at 36,37°C. Adenine nucleotides were determined by HPLC. Under physiological conditions (4.3 mM ATP in the pipette solution, ATPi) IK(ATP) did not contribute to basal electrical activity. The ATP-dependent potassium (K(ATP)) channel opener pinacidil activated IK(ATP) dependent on [ATP]i showing a significantly more pronounced activation at lower (1 mM) [ATP]i. Supplementation of cardiomyocytes with 300 ,g ml,1 NADH (4,6 h) resulted in a significantly reduced IK(ATP) activation by pinacidil compared to control cells. The current density was 13.8±3.78 (n=6) versus 28.9±3.38 pA pF,1 (n=19; P<0.05). Equimolar amounts of the related compounds nicotinamide and NAD+ did not achieve a similar effect like NADH. Measurement of adenine nucleotides by HPLC revealed a significant increase in intracellular ATP (NADH supplementation: 45.6±1.88 nmol mg,1 protein versus control: 35.4±2.57 nmol mg,1 protein, P<0.000005). These data show that supplementation of guinea-pig ventricular cardiomyocytes with NADH results in a decreased activation of IK(ATP) by pinacidil compared to control myocytes, indicating a higher subsarcolemmal ATP concentration. Analysis of intracellular adenine nucleotides by HPLC confirmed the significant increase in ATP. British Journal of Pharmacology (2003) 139, 749,754. doi:10.1038/sj.bjp.0705300 [source]

The mechanism of improved sodium homeostasis of low-dose losartan in preascitic cirrhosis

HEPATOLOGY, Issue 6 2002
Florence Wong 200 Elizabeth St.
Renal sodium retention on standing is one aspect of the abnormal renal sodium handling in preascitic, well-compensated patients with cirrhosis. Recently, it has been shown that low doses (7.5 mg) of the angiotensin II (Ang II) receptor antagonist, losartan, can reverse renal sodium retention on high, 200-mmol sodium/d diet in these patients and restore them to sodium balance. Therefore, the effect of 7.5 mg of losartan on sodium excretion, when changing from supine to erect posture for 2 hours, was examined in 10 well-compensated patients with cirrhosis and 9 age- and sex-matched controls on the same sodium diet, under strictly controlled metabolic conditions. In contrast to control subjects, in whom sodium excretion was unaffected, single 7.5-mg doses of losartan again restored the preascitic patients with cirrhosis to sodium balance. In addition, it blunted the fall in erect posture, induced renal sodium excretion by a reduction in proximal and distal tubular reabsorption of sodium. These changes occurred without any significant changes in blood volumes, systemic and renal hemodynamics, or glomerular filtration rate (GFR) and filtered sodium load compared with controls, and despite activation of the systemic renin-angiotensin-aldosterone system, which was still within normal levels. In conclusion, the beneficial natriuretic effects of low-dose losartan on erect posture , induced sodium retention in preascitic cirrhosis supports the suggestion that the pathophysiology of sodium retention in preascites is in part caused by an intrarenal tubular effect of Ang II in that posture. [source]

Metabolic syndrome and mitochondrial function: Molecular replacement and antioxidant supplements to prevent membrane peroxidation and restore mitochondrial function,

Garth L. Nicolson
Abstract Metabolic syndrome consists of a cluster of metabolic conditions, such as hypertriglyeridemia, hyper-low-density lipoproteins, hypo-high-density lipoproteins, insulin resistance, abnormal glucose tolerance and hypertension, that,in combination with genetic susceptibility and abdominal obesity,are risk factors for type 2 diabetes, vascular inflammation, atherosclerosis, and renal, liver and heart disease. One of the defects in metabolic syndrome and its associated diseases is excess cellular oxidative stress (mediated by reactive oxygen and nitrogen species, ROS/RNS) and oxidative damage to mitochondrial components, resulting in reduced efficiency of the electron transport chain. Recent evidence indicates that reduced mitochondrial function caused by ROS/RNS membrane oxidation is related to fatigue, a common complaint of MS patients. Lipid replacement therapy (LRT) administered as a nutritional supplement with antioxidants can prevent excess oxidative membrane damage, restore mitochondrial and other cellular membrane functions and reduce fatigue. Recent clinical trials have shown the benefit of LRT plus antioxidants in restoring mitochondrial electron transport function and reducing moderate to severe chronic fatigue. Thus LRT plus antioxidant supplements should be considered for metabolic syndrome patients who suffer to various degrees from fatigue. J. Cell. Biochem. 100: 1352,1369, 2007. © 2007 Wiley-Liss, Inc. [source]

Mechanistic understanding of the fermentative L -glutamic acid overproduction by Corynebacterium glutamicum through combined metabolic flux profiling and transmembrane transport characteristics

Theodora Tryfona
Abstract Since the 1950s when Micrococcus glutamicus later renamed Corynebacterium glutamicum was discovered, the production of amino acids by fermentative methods has become an important aspect of industrial microbiology. Numerous studies to understand and improve the metabolic conditions leading to amino acid overproduction have been carried out. Most amino acids are currently produced by use of mutants that contain combinations of auxotrophic and regulatory mutations. L -Glutamic acid is the amino acid produced in the greatest quantities (106 tonnes per year) and Corynebacteria are central to its industrial production. However, further improvements to strain performance are difficult to obtain by empirical optimization and a more rational approach is required. The use of metabolic flux analysis provides valuable information regarding bottlenecks in the formation of desired metabolites. Such techniques have found application in elucidating flux control, provided insight into metabolic network function and developed methods to amplify or redirect fluxes in engineered bioprocesses. Hence, branch points in biosynthesis, precursor supply in fuelling reactions and export of metabolites can be manipulated, resulting in high glutamic acid overproduction by Corynebacterium glutamicum fermentations. In this review, in addition to reviewing the state of play in metabolic flux analysis for glutamate overproduction, the metabolic pathways involved in the production of L -glutamic acid, the mechanisms mediating its efflux and secretion as well as their manipulation to achieve higher glutamate production, are discussed. The link between metabolic flux and transmembrane transport of glutamic acid are also considered. Copyright © 2004 Society of Chemical Industry [source]

Non-alcoholic fatty liver syndrome: A hepatic consequence of common metabolic diseases

Abstract Background and Aims: The association of liver steatosis with a number of common metabolic conditions has been suggested. The aim of the present study was to evaluate the clinical features of subjects with different severities of steatosis. Methods: The present study was performed in 282 consecutive patients with ,bright liver' at ultrasonography and in 58 subjects without steatosis. They had no history of alcohol abuse and negative tests for the presence of hepatitis B and C virus. Patients underwent clinical examination, anthropometry, laboratory tests and routine liver ultrasonography. Steatosis was graded as absent, mild, moderate and severe. Results: A progressive increase in the prevalence of obesity (P < 0.001), type 2 diabetes (P < 0.001), alanine aminotransferase (ALT) elevation (P < 0.001) and hypertriglyceridemia (P < 0.001), and a decrease of hypercholesterolemia (P < 0.05) was observed from the control group to the groups with mild, moderate and severe steatosis. More than half the subjects with liver steatosis had insulin resistance metabolic syndrome. Obesity, diabetes and hypertriglyceridemia were more common by 5.3-fold, 4.0-fold, and 6.7-fold, respectively, in subjects with severe steatosis, as compared to controls. Prevalence of obesity, diabetes and hyperlipidemia was significantly higher in subjects with fatty liver and ALT elevation. Conclusion: Fatty liver can be considered as the hepatic consequence of common metabolic diseases. © 2003 Blackwell Publishing Asia Pty Ltd [source]

Hibernation as a far-reaching program for the modulation of RNA transcription

Manuela Malatesta
Abstract In eukaryotic cells, pre-mRNAs undergo several transformation steps to generate mature mRNAs ready to be exported to the cytoplasm. The molecular and structural apparatus for mRNA production is generally able to promptly respond to variations of metabolic demands. Hibernating mammals, which periodically enter a hypometabolic state, represent an interesting physiological model to investigate the adaptive morpho-functional modifications of the pre-mRNA transcriptional and processing machinery under extreme metabolic conditions. In this study, the subnuclear distribution of some transcriptional, splicing, and cleavage factors was investigated by ultrastructural immunocytochemistry in cell nuclei of the liver (a highly metabolizing organ involved in multiple regulatory functions) and the brown adipose tissue (responsible for nonshivering thermogenesis) from euthermic, hibernating, and arousing hazel dormice (Muscardinus avellanarius). Our observations demonstrate that, during hibernation, transcriptional activity significantly decreases and pre-mRNA processing factors undergo an intranuclear redistribution moving to domains usually devoid of such molecules; moreover, in hepatocytes, there is a preferential accumulation of pre-mRNAs at the splicing stage, whereas, in brown adipocytes, pre-mRNAs are mainly stored at the cleavage stage. Upon arousal, the pre-mRNAs at the cleavage stage are immediately utilized, while the maturation of pre-mRNAs at the splicing stage seems to be restored before transcription had taken place. Our data suggest a programmed intranuclear reorganization of the RNA maturation machinery aimed at efficiently and rapidly restoring the pre-mRNA processing, and, consequently, the specific cellular activities upon arousal. Once again natural hibernation appears as a highly programmed hypometabolic state rather than a simple fall of metabolic and physiological functions. Microsc. Res. Tech., 2008. © 2008 Wiley-Liss, Inc. [source]

Quadriparesis as initial presentation of hyperosmolar non-ketotic diabetes


Abstract Acute onset quadriparesis can be a manifestation of a variety of neurological and metabolic conditions. We report the case of a 47-year-old alcoholic gentleman who presented with acute onset weakness of all four limbs associated with hypokalemia and very high blood glucose (hyperosmolar nonketotic diabetes,HNKD) detected for the first time. He was confirmed as having type 2 diabetes (detectable insulin and C-peptide levels) and his quadriparesis completely resolved on potassium replacement and treatment with insulin. HNKD is discussed along with the possible mechanisms of hypokalemia in this patient presenting with reversible limb weakness as an initial manifestation of type 2 diabetes. Copyright © 2002 John Wiley & Sons, Ltd. [source]

The biomolecule ubiquinone exerts a variety of biological functions,

BIOFACTORS, Issue 1-4 2003
Hans Nohl
Abstract The chemistry of ubiquinone allows reversible addition of single electrons and protons. This unique property is used in nature for aerobic energy gain, for unilateral proton accumulation, for the generation of reactive oxygen species involved in physiological signaling and a variety of pathophysiological events. Since several years ubiquinone is also considered to play a major role in the control of lipid peroxidation, since this lipophilic biomolecule was recognized to recycle ,-tocopherol radicals back to the chain-breaking form, vitamin E. Ubiquinone is therefore a biomolecule which has increasingly focused the interest of many research groups due to its alternative pro- and antioxidant activity. We have intensively investigated the role of ubiquinone as prooxidant in mitochondria and will present experimental evidences on conditions required for this function, we will also show that lysosomal ubiquinone has a double function as proton translocator and radical source under certain metabolic conditions. Furthermore, we have addressed the antioxidant role of ubiquinone and found that the efficiency of this activity is widely dependent on the type of biomembrane where ubiquinone exerts its chain-breaking activity. [source]

Forelimb postischaemic reactive hyperaemia is impaired by hypotensive low body negative pressure in healthy subjects

Marc Charles
Summary Local metabolic conditions adapt blood supply to metabolic requirement by a direct effect on vascular smooth muscles and indirectly by modulating sympathetic vasoconstrictor effectiveness. During exercise, sympathetic nervous activity could in turn interfere on local metabolic control of vascular tone and restrain blood flow to active muscles. In order to investigate that interaction non-invasively, we measured postischaemic reactive hyperaemia (RH) in the forelimb of eight healthy young men (22·7 ± 2·1 years) at rest and during two levels of sympathetic stimulation using low body negative pressure (LBNP ,15 and ,30 mmHg). During every stages, RH was measured after 40, 60, 90 and 180 s of arterial occlusion, respectively. In control conditions, RH rose with duration of ischaemia (18·9, 24·2, 30·4, 33·1 ml min,1 per 100 ml,1 for 40, 60, 90 and 180 s of ischaemia, respectively). During non-hypotensive LBNP (,15 mmHg) sympathetic activation was associated with decreased forelimb blood flow (6·4 ± 0·9 versus 3·9 ± 0·6 ml min,1 per 100 ml,1, P<0·01), but RH were not significantly different from control conditions. During hypotensive tachycardia LBNP (,30 mmHg), RH were significantly lower than under the previous LBNP stage. This fall in RH was greater after the shortest gap of ischaemia and tapered off as arterial occlusion gap increased (,22·3, ,13·1, ,10·5 and ,8·7% for 40, 60, 90 and 180 s of ischaemia, respectively). These results suggested that vascular tone adaptation to local metabolic conditions was modified by sympathetic nervous activation. This was particularly marked when an hypotensive-mediated sympathetic stimulation was opposed to short gaps of ischaemia. [source]