scholarly journals Glycogenolysis in Astrocytes Supports Blood-Borne Glucose Channeling Not Glycogen-Derived Lactate Shuttling to Neurons: Evidence from Mathematical Modeling

2010 ◽  
Vol 30 (12) ◽  
pp. 1895-1904 ◽  
Author(s):  
Mauro DiNuzzo ◽  
Silvia Mangia ◽  
Bruno Maraviglia ◽  
Federico Giove

In this article, we examined theoretically the role of human cerebral glycogen in buffering the metabolic requirement of a 360-second brain stimulation, expanding our previous modeling study of neurometabolic coupling. We found that glycogen synthesis and degradation affects the relative amount of glucose taken up by neurons versus astrocytes. Under conditions of 175:115 mmol/L (∼1.5:1) neuronal versus astrocytic activation-induced Na+ influx ratio, ∼12% of astrocytic glycogen is mobilized. This results in the rapid increase of intracellular glucose-6-phosphate level on stimulation and nearly 40% mean decrease of glucose flow through hexokinase (HK) in astrocytes via product inhibition. The suppression of astrocytic glucose phosphorylation, in turn, favors the channeling of glucose from interstitium to nearby activated neurons, without a critical effect on the concurrent intercellular lactate trafficking. Under conditions of increased neuronal versus astrocytic activation-induced Na+ influx ratio to 190:65 mmol/L (∼3:1), glycogen is not significantly degraded and blood glucose is primarily taken up by neurons. These results support a role for astrocytic glycogen in preserving extracellular glucose for neuronal utilization, rather than providing lactate to neurons as is commonly accepted by the current ‘thinking paradigm’. This might be critical in subcellular domains during functional conditions associated with fast energetic demands.

2002 ◽  
Vol 93 (2) ◽  
pp. 765-772 ◽  
Author(s):  
Eva Tomás ◽  
Antonio Zorzano ◽  
Neil B. Ruderman

Over the past 30 years, a considerable body of evidence has revealed that a prior bout of exercise can increase the ability of insulin to stimulate glucose transport and glycogen synthesis in skeletal muscle. Apart from its clinical implications, this work has led to a considerable effort to determine at a molecular level how exercise causes this effect and, in particular, whether it does so by enhancing specific events in the insulin-signaling cascade. The objective of this review is to discuss from a historical perspective how our current thinking in this area has evolved and the people responsible for it. Areas to be discussed include the effect or lack of effect of prior exercise on the insulin-signaling pathway, effects of exercise on the regulation by insulin of the GLUT-4 glucose transporter in muscle, and the emerging role of AMP-activated protein kinase as a mediator of exercise-induced signaling events. In addition, we will discuss briefly some of the avenues that research in this area is likely to follow.


Author(s):  
Clement Guitton

Attribution — tracing those responsible for a cyber attack — is of primary importance when classifying it as a criminal act, an act of war, or an act of terrorism. Three assumptions dominate current thinking: attribution is a technical problem; it is unsolvable; and it is unique. Approaching attribution as a problem forces us to consider it either as solved or unsolved. Yet attribution is far more nuanced, and is best approached as a process in constant flux, driven by judicial and political pressures. In the criminal context, courts must assess the guilt of criminals, mainly based on technical evidence. In the national security context, decision-makers must analyze unreliable and mainly non-technical information in order to identify an enemy of the state. Attribution in both contexts is political: in criminal cases, laws reflect society’s prevailing norms and powers; in national security cases, attribution reflects a state’s will to maintain, increase or assert its power. However, both processes differ on many levels. The constraints, which reflect common aspects of many other political issues, constitute the structure of the book: the need for judgment calls, the role of private companies, the standards of evidence, the role of time, and the plausible deniability of attacks.


1956 ◽  
Vol 184 (2) ◽  
pp. 296-300 ◽  
Author(s):  
László Kátó ◽  
Béla Gözsy

Experiments are presented to the effect that in an inflammatory process histamine and leucotaxin appear successively at different and orderly time intervals, thus assuring an increased fluid flow through the capillary wall. Histamine is released not only in the inflammatory process but also by intradermal administration of such substances (volatile oils or their components) which induce neither the triple response of Th. Lewis nor any tissue damage. This could be explained by the fact that in the tissues histamine is ‘present’ but leucotaxin is ‘formed.’


Nutrients ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 1104
Author(s):  
Cong Xie ◽  
Weikun Huang ◽  
Richard L. Young ◽  
Karen L. Jones ◽  
Michael Horowitz ◽  
...  

Bile acids are cholesterol-derived metabolites with a well-established role in the digestion and absorption of dietary fat. More recently, the discovery of bile acids as natural ligands for the nuclear farnesoid X receptor (FXR) and membrane Takeda G-protein-coupled receptor 5 (TGR5), and the recognition of the effects of FXR and TGR5 signaling have led to a paradigm shift in knowledge regarding bile acid physiology and metabolic health. Bile acids are now recognized as signaling molecules that orchestrate blood glucose, lipid and energy metabolism. Changes in FXR and/or TGR5 signaling modulates the secretion of gastrointestinal hormones including glucagon-like peptide-1 (GLP-1) and peptide YY (PYY), hepatic gluconeogenesis, glycogen synthesis, energy expenditure, and the composition of the gut microbiome. These effects may contribute to the metabolic benefits of bile acid sequestrants, metformin, and bariatric surgery. This review focuses on the role of bile acids in energy intake and body weight, particularly their effects on gastrointestinal hormone secretion, the changes in obesity and T2D, and their potential relevance to the management of metabolic disorders.


1999 ◽  
Vol 266 (1-4) ◽  
pp. 420-424 ◽  
Author(s):  
U.M.S. Costa ◽  
J.S.Andrade Jr. ◽  
H.A. Makse ◽  
H.E. Stanley

2005 ◽  
Vol 187 (24) ◽  
pp. 8322-8331 ◽  
Author(s):  
Renate Dippel ◽  
Winfried Boos

ABSTRACT The maltose/maltodextrin regulon of Escherichia coli consists of 10 genes which encode a binding protein-dependent ABC transporter and four enzymes acting on maltodextrins. All mal genes are controlled by MalT, a transcriptional activator that is exclusively activated by maltotriose. By the action of amylomaltase, we prepared uniformly labeled [14C]maltodextrins from maltose up to maltoheptaose with identical specific radioactivities with respect to their glucosyl residues, which made it possible to quantitatively follow the rate of transport for each maltodextrin. Isogenic malQ mutants lacking maltodextrin phosphorylase (MalP) or maltodextrin glucosidase (MalZ) or both were constructed. The resulting in vivo pattern of maltodextrin metabolism was determined by analyzing accumulated [14C]maltodextrins. MalP− MalZ+ strains degraded all dextrins to maltose, whereas MalP+ MalZ− strains degraded them to maltotriose. The labeled dextrins were used to measure the rate of transport in the absence of cytoplasmic metabolism. Irrespective of the length of the dextrin, the rates of transport at a submicromolar concentration were similar for the maltodextrins when the rate was calculated per glucosyl residue, suggesting a novel mode for substrate translocation. Strains lacking MalQ and maltose transacetylase were tested for their ability to accumulate maltose. At 1.8 nM external maltose, the ratio of internal to external maltose concentration under equilibrium conditions reached 106 to 1 but declined at higher external maltose concentrations. The maximal internal level of maltose at increasing external maltose concentrations was around 100 mM. A strain lacking malQ, malP, and malZ as well as glycogen synthesis and in which maltodextrins are not chemically altered could be induced by external maltose as well as by all other maltodextrins, demonstrating the role of transport per se for induction.


1960 ◽  
Vol 82 (4) ◽  
pp. 921-927 ◽  
Author(s):  
Friedrich O. Ringleb

The conditions for the equilibrium of two vortexes in a two-dimensional flow through a duct or diffuser are derived. Potential-flow considerations and a few basic results from viscous-flow theory are used for the discussion of the role of cusps as separation control and trapping devices for standing vortexes. The investigations are applied to cusp diffusers especially with regard to the wind tunnel of the James Forrestal Research Center of Princeton University.


1990 ◽  
Vol 70 (2) ◽  
pp. 331-390 ◽  
Author(s):  
J. I. Hoffman ◽  
J. A. Spaan

The blood vessels that run on the surface of the heart and through its muscle are compliant tubes that can be affected by the pressures external to them in at least two ways. If the pressure outside these vessels is higher than the pressure at their downstream ends, the vessels may collapse and become Starling resistors or vascular waterfalls. If this happens, the flow through these vessels depends on their resistance and the pressure drop from their inflow to the pressure around them and is independent of the actual downstream pressure. In the first part of this review, the physics of collapsible tubes is described, and the possible occurrences of vascular waterfalls in the body is evaluated. There is good evidence that waterfall behavior is seen in collateral coronary arteries and in extramural coronary veins, but the evidence that intramural coronary vessels act like vascular waterfalls is inconclusive. There is no doubt that in systole there are high tissue pressures around the intramyocardial vessels, particularly in the subendocardial muscle of the left ventricle. The exact nature and values of the forces that act at the surface of the small intramural vessels, however, are still not known. We are not certain whether radial (compressive) or circumferential and longitudinal (tensile) stresses are the major causes of vascular compression; the role of collagen struts in modifying the reaction of vessel walls to external pressures is unknown but possibly important; direct examination of small subepicardial vessels has failed to show vascular collapse. One of the arguments in favor of intramyocardial vascular waterfalls has been that during a long diastole the flow in the left coronary artery decreases and reaches zero when coronary arterial pressure is still high: it can be as much as 50 mmHg in the autoregulating left coronary arterial bed and approximately 15-20 mmHg even when the vessels have been maximally dilated. These high zero flow pressures, especially during maximal vasodilatation, have been regarded as indicating a high back pressure to flow that is due to waterfall behavior of vessels that are exposed to tissue pressures.(ABSTRACT TRUNCATED AT 400 WORDS)


2016 ◽  
Vol 10 (10) ◽  
pp. 180 ◽  
Author(s):  
Hung Duc Pham ◽  
Ravi Fotedar ◽  
Chau Minh Nguyen ◽  
Muhammad Abu Bakar Siddik

The dietary selenium (Se) requirement has been determined for cobia Rachycentron canadum using purified diet; however, its role in the utilisation of plant-derived ingredients has not been evaluated in the species. Therefore, a 3 x 2 factorial experimental design involving three inclusion levels (0, 210 and 315 g/kg) of lupin Lupinus angustifolius kernel meal (LKM) and two concentrations (0 and 0.8 mg/kg) of Se was used to evaluate the effects of Se supplementation in conjunction with LKM on the growth, feed utilisation and physiological responses in the cobia. Six isonitrogenous (46.5 % crude protein) and isoenergetic (21 MJ/kg gross energy) diets were formulated and fed to cobia for 7 weeks in a flow-through seawater system. The results showed significant effects of Se supplementation and its interaction with dietary lupin on the growth and feed efficiency of cobia. Se supplementation significantly improved the growth and feed utilisation efficiency in cobia fed lupin-based diets. The nutrient digestibility of fish fed supplemental Se lupin-based diets was significantly higher than that of fish fed diets without Se supplementation at each inclusion level of LKM. There were no significant effects of dietary Se supplementation on the survival, muscle composition or muscle amino acids, whereas regression analysis indicated a positive linear relationship between tissue Se accumulation and dietary Se levels. An enhancement of haematological responses was also observed in cobia fed Se-supplemented diets. In summary, cobia fed lupin-based diets required higher dietary Se supplementation for higher feed utilisation efficiency than previously quantified for the casein-based diet.


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