scholarly journals Hexose metabolism in pancreatic islets. Inhibition of hexokinase

1984 ◽  
Vol 223 (2) ◽  
pp. 447-453 ◽  
Author(s):  
M H Giroix ◽  
A Sener ◽  
D G Pipeleers ◽  
W J Malaisse
Keyword(s):  
Major Fraction ◽  
Intracellular Space ◽  
Extracellular Glucose ◽  
Low Glucose ◽  
Glucose Phosphorylation ◽  
Metabolic Data ◽  
A Minor ◽  
Glycolytic Rate ◽  
State Content ◽  
Hexose Metabolism

In islet homogenates, hexokinase-like activity (Km 0.05 mM; Vmax. 1.5 pmol/min per islet) accounts for the major fraction of glucose phosphorylation. Yet the rate of glycolysis in intact islets incubated at low glucose concentrations (e.g. 1.7 mM) sufficient to saturate hexokinase only represents a minor fraction of the glycolytic rate observed at higher glucose concentrations. This apparent discrepancy between enzymic and metabolic data may be attributable, in part at least, to inhibition of hexokinase in intact islets. Hexokinase, which is present in both islet and purified B-cell homogenates, is indeed inhibited by glucose 6-phosphate (Ki 0.13 mM) and glucose 1,6-bisphosphate (Ki approx. 0.2 mM), but not by fructose 2,6-bisphosphate. In intact islets, the steady-state content of glucose 6-phosphate (0.26-0.79 pmol/islet) and glucose 1,6-bisphosphate (5-48 fmol/islet) increases, in a biphasic manner, at increasing concentrations of extracellular glucose (up to 27.8 mM). From these measurements and the intracellular space of the islets, it was estimated that the rate of glucose phosphorylation as catalysed by hexokinase represents, in intact islets, no more than 12-24% of its value in islet homogenates.

scholarly journals Control of glucose phosphorylation in L6 myotubes by compartmentalization, hexokinase, and glucose transport

2003 ◽  
Vol 370 (1) ◽  
pp. 47-56 ◽  
Author(s):  
Richard R. WHITESELL ◽  
Hossein ARDEHALI ◽  
Richard L. PRINTZ ◽  
Joseph M. BEECHEM ◽  
Susan M. KNOBEL ◽  
...  
Keyword(s):  
Glucose Transport ◽  
Insulin Action ◽  
Cytochalasin B ◽  
L6 Myotubes ◽  
Test Models ◽  
Different Types ◽  
Extracellular Glucose ◽  
Low Glucose ◽  
Glucose Phosphorylation ◽  
Intracellular Glucose

In muscle, insulin enhances influx of glucose and its conversion to glucose 6-phosphate (G6P) by hexokinase (HK). While effects of insulin on glucose transport have been demonstrated, its effect on the activity of HK of cells has not. In L6 myotubes treated for 24h with insulin there was increased expression of the HK isoform, HKII, and increased glucose phosphorylation without a concomitant increase in glucose transport, indirectly suggesting that phosphorylation of glucose was a target of insulin action [Osawa, Printz, Whitesell and Granner (1995) Diabetes 44, 1426—1432]. In the present work the same treatment led to a 2-fold rise in G6P, suggesting that transport and/or HK were important targets of insulin action. We used a method to identify the site of rate control involving the specificity of phosphorylation towards 2-deoxy-[1-14C]glucose and d-[2-3H]glucose. Glucose transport does not greatly discriminate between these two tracers while HK shows increased specificity for glucose. Specificity of the glucose phosphorylation of the cells increased with addition of insulin and when extracellular glucose was raised. Specificity was reduced at low glucose concentrations or when the inhibitor of transport, cytochalasin B, was added. We conclude that transport and HK share nearly equal control over glucose phosphorylation in these cells. A computer program was used to test models for compatibility with the different types of experiments. The predicted intracellular glucose and transport rates associated with phosphorylation activity were lower than their measured values for the whole cell. In the most likely model, 15±4% of the glucose transporters serve a proportionate volume of the cytoplasm. Insulin activation of glucose phosphorylation might then result from stimulation of these transporters together with HK recruitment or relief from inhibition by G6P.

scholarly journals Inhibition of mitochondrial function by metformin increases glucose uptake, glycolysis and GDF-15 release from intestinal cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ming Yang ◽  
Tamana Darwish ◽  
Pierre Larraufie ◽  
Debra Rimmington ◽  
Irene Cimino ◽  
...  
Keyword(s):  
Mitochondrial Dysfunction ◽  
Glucose Uptake ◽  
Intestinal Cell ◽  
Cell Physiology ◽  
Sequencing Analysis ◽  
Extracellular Acidification ◽  
Type2 Diabetes ◽  
Site Of Action ◽  
Glycolytic Rate ◽  
Hexose Metabolism

AbstractEven though metformin is widely used to treat type2 diabetes, reducing glycaemia and body weight, the mechanisms of action are still elusive. Recent studies have identified the gastrointestinal tract as an important site of action. Here we used intestinal organoids to explore the effects of metformin on intestinal cell physiology. Bulk RNA-sequencing analysis identified changes in hexose metabolism pathways, particularly glycolytic genes. Metformin increased expression of Slc2a1 (GLUT1), decreased expression of Slc2a2 (GLUT2) and Slc5a1 (SGLT1) whilst increasing GLUT-dependent glucose uptake and glycolytic rate as observed by live cell imaging of genetically encoded metabolite sensors and measurement of oxygen consumption and extracellular acidification rates. Metformin caused mitochondrial dysfunction and metformin’s effects on 2D-cultures were phenocopied by treatment with rotenone and antimycin-A, including upregulation of GDF15 expression, previously linked to metformin dependent weight loss. Gene expression changes elicited by metformin were replicated in 3D apical-out organoids and distal small intestines of metformin treated mice. We conclude that metformin affects glucose uptake, glycolysis and GDF-15 secretion, likely downstream of the observed mitochondrial dysfunction. This may explain the effects of metformin on intestinal glucose utilisation and food balance.

Implantation of Nitrogen into Ti/Al, Ni/Ti, and Ni/Al Bilayers

1991 ◽  
Vol 235 ◽  
Author(s):  
D. O. Boerma ◽  
T. Corts
Keyword(s):  
Nuclear Reaction Analysis ◽  
Si Substrate ◽  
Major Fraction ◽  
High Chemical ◽  
Gaussian Shape ◽  
Depth Profiles ◽  
Implantation Temperature ◽  
Projected Range ◽  
A Minor ◽  
Metal Layers

ABSTRACTTi/Al, Ni/Ti, and Ni/Al bilayers were produced by evaporation on a Si substrate. The thicknesses of the composing layers were in the 50–200 nm range. The as-evaporated bilayers were implanted with doses of 0.4–2.5 · 1017 of 15N ions/cm2. The 15N energy was chosen so that the calculated projected range was either in the middle of the top Ni layer, or coincided with the interface between the metal layers. The implantation temperature was varied in the range from 25 °C to 245 °C. The 15N depth profiles as measured with nuclear reaction analysis (NRA) were found to have the expected Gaussian shape for the Ti/Al bilayers. However, in the Ni/Ti and Ni/Al layers very asymmetric 15N profiles were observed, with a major fraction of N atoms in the Ti or Al layer, and a minor fraction in the Ni layer. The N concentrations in the Al or Ti layers were found to be almost constant. A massive redistribution of N atoms must have taken place in all three metals during the implantations, to form the observed profiles. We speculate that this remarkable phenomenon, which occurs even below 80°C, can be explained by interstitial diffusion of N atoms and subsequent trapping in Ti or Al, which have a high chemical affinity for nitrogen. The N atoms remaining in the Ni layer after implantation were found to migrate out of this layer during annealing at temperatures ≥250°C.

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
Keyword(s):  
Glycogen Synthesis ◽  
Product Inhibition ◽  
Current Thinking ◽  
Metabolic Requirement ◽  
Previous Modeling Study ◽  
Extracellular Glucose ◽  
Subcellular Domains ◽  
Glucose Phosphorylation ◽  
Flow Through

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.

scholarly journals Phosphotyrosine phosphatase associated with band 3 protein in the human erythrocyte membrane

1996 ◽  
Vol 314 (3) ◽  
pp. 881-887 ◽  
Author(s):  
Yehudit ZIPSER ◽  
Nechama S. KOSOWER
Keyword(s):  
Erythrocyte Membrane ◽  
Human Erythrocyte ◽  
Intact Cell ◽  
Band 3 ◽  
Band 3 Protein ◽  
Human Erythrocyte Membrane ◽  
Major Fraction ◽  
Phosphotyrosine Phosphatase ◽  
A Minor ◽  
Triton X

The anion-exchange band 3 protein is the main erythrocyte protein that is phosphorylated by tyrosine kinase. To study the regulation of band 3 phosphorylation, we examined phosphotyrosine phosphatase (PTP) activity in the human erythrocyte. We show that the human erythrocyte membrane contains a band 3-associated neutral PTP which is activated by Mg2+ and inhibited by Mn2+ and vanadate. The PTP is active in the intact cell and in the isolated membrane. A major fraction of the PTP is tightly bound to the membrane and can be extracted from it by Triton X-100; a minor part is associated with the Triton X-100-insoluble cytoskeleton. The behaviour of the PTP parallels that of band 3, the major fraction of which is extractable by detergents with a minor fraction being anchored to the cytoskeleton. Moreover, band 3 is co-precipitated when the PTP is immunoprecipitated from solubilized membranes, and PTP is co-precipitated when band 3 is immunoprecipitated. The PTP appears to be related to PTP1B (identified using an antibody to an epitope in its catalytic domain and by molecular mass). The system described here has a unique advantage for PTP research, since it allows the study of the interaction of a PTP with an endogenous physiological substrate that is present in substantial amounts in the cell membrane. The membrane-bound, band 3-associated, PTP may play a role in band 3 function in the erythrocyte and in other cells which have proteins analogous to band 3.

Kinetics of glucose transport and sequestration in lactating bovine mammary glands measured in vivo with a paired indicator/nutrient dilution technique

2005 ◽  
Vol 99 (3) ◽  
pp. 799-806 ◽  
Author(s):  
Fulong Qiao ◽  
Donald R. Trout ◽  
Changting Xiao ◽  
John P. Cant
Keyword(s):  
Glucose Transport ◽  
Goodness Of Fit ◽  
Mammary Glands ◽  
Integration Model ◽  
Intracellular Space ◽  
First Order ◽  
Extracellular Glucose ◽  
Kinetics Of ◽  
Dilution Curves

To quantify kinetics of mammary glucose utilization in vivo, 24 paired glucose and extracellular indicator ( p-aminohippuric acid) dilution curves across intact bovine mammary glands were obtained after bolus injections into the external iliac artery. Dilution curves were analyzed using a compartmental capillary, convolution integration model. Four candidate submodels of glucose transport and metabolism in capillary supply zones were fit to the glucose dilution curves and evaluated. Model I, with one extracellular compartment for glucose and first-order unidirectional uptake, failed, indicating that efflux of glucose from the intracellular space could not be ignored. Model II, with first-order exchanges between extracellular and intracellular compartments and sequestration from the latter, was overdefined because unidirectional clearance of glucose was at least five times the blood flow rate and 20 times the net clearance rate. Model III, combining extracellular and intracellular space into one compartment, was superior in its goodness-of-fit to curves and identifiability of parameters. Michaelis-Menten parameters of sequestration were not identifiable. Parameters of the optimal compartmental capillary, convolution integration model were applicable to both the dynamics of injected glucose dilution and the steady-state background arteriovenous difference of glucose. Glucose sequestration followed first-order kinetics between 0 and 7 mM extracellular glucose with an average rate constant of 0.006 s−1 or a clearance of 44 ml/s. The ratio of intracellular to extracellular glucose distribution space was 0.34, which is considerably lower than the expected intracellular volume and suggests an intracellular occlusion compartment with which extracellular glucose rapidly exchanges.

scholarly journals Regulation of Fructose 1,6-Bisphosphatase in Procyclic Form Trypanosoma brucei

Pathogens ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 617
Author(s):  
Christina Wilkinson ◽  
Meredith T. Morris
Keyword(s):  
Trypanosoma Brucei ◽  
Post Translational Modifications ◽  
Procyclic Form ◽  
Protein Levels ◽  
Glucose Levels ◽  
Fructose 1,6 Bisphosphatase ◽  
Extracellular Glucose ◽  
Low Glucose ◽  
The Relationship

Glycolysis is well described in Trypanosoma brucei, while the importance of gluconeogenesis and one of the key enzymes in that pathway, fructose 1,6-bisphosphatase, is less understood. Using a sensitive and specific assay for FBPase, we demonstrate that FBPase activity in insect stage, procyclic form (PF), parasite changes with parasite cell line, extracellular glucose levels, and cell density. FBPase activity in log phase PF 2913 cells was highest in high glucose conditions, where gluconeogenesis is expected to be inactive, and was undetectable in low glucose, where gluconeogenesis is predicted to be active. This unexpected relationship between FBPase activity and extracellular glucose levels suggests that FBPase may not be exclusively involved in gluconeogenesis and may play an additional role in parasite metabolism. In stationary phase cells, the relationship between FBPase activity and extracellular glucose levels was reversed. Furthermore, we found that monomorphic PF 2913 cells had significantly higher FBPase levels than pleomorphic PF AnTat1.1 cells where the activity was undetectable except when cells were grown in standard SDM79 media, which is glucose-rich and commonly used to grow PF trypanosomes in vitro. Finally, we observed several conditions where FBPase activity changed while protein levels did not, suggesting that the enzyme may be regulated via post-translational modifications.

XAFS Study of Fe K Edge in Al2O3-B2O3-Fe2O3-Na2O-SiO2 Glasses

2013 ◽  
Vol 1518 ◽  
pp. 59-64 ◽  
Author(s):  
S.V. Stefanovsky ◽  
A.A. Shiryaev ◽  
Y.V. Zubavichus ◽  
K.M. Fox ◽  
J.C. Marra
Keyword(s):  
Coordination Number ◽  
Valence State ◽  
Local Environment ◽  
Homogeneous Distribution ◽  
Major Fraction ◽  
Minor Fraction ◽  
State And Local ◽  
A Minor ◽  
Fe Ions

ABSTRACTValence state and local environment of Fe in complex glasses related to the system Al2O3-B2O3-Fe2O3-Na2O-SiO2 were studied. In all the glasses, the major fraction of Fe exists as Fe3+ ions but a minor fraction of Fe2+ ions especially in the glass with the lowest K=[SiO2]/[B2O3] ratio was also present. Average Fe—O distance in the first shell is 1.80-1.85 Å and coordination number is 4-6. The intensity due to the second sphere is rather weak demonstrating homogeneous distribution of Fe ions in the glass.

Water Debinding for Zirconia Powder Injection Molding

2008 ◽  
Vol 368-372 ◽  
pp. 732-735 ◽  
Author(s):  
Zhi Peng Xie ◽  
Lin Lin Wang ◽  
Xian Feng Yang ◽  
Zhen Ting Zhang
Keyword(s):  
Polyethylene Glycol ◽  
Injection Molding ◽  
Powder Injection ◽  
Major Fraction ◽  
Zirconia Powder ◽  
Sintered Ceramic ◽  
Molecular Weights ◽  
Minor Fraction ◽  
Ceramic Injection Molding ◽  
A Minor

Water debinding is an important debinding technique for ceramic injection molding. However cracks or blisters usually generate during water extraction. In this paper, two types of multi-component binder systems were studied: (1) a major fraction of polyethylene glycol (PEG), and a minor fraction of polyvinyl butyra (PVB) and other additives. (2) a major fraction of PEG, and a minor fraction of polymethyl methacrylate (PMMA) and other additives. Mechanism of defects generation was investigated, and PEGs with various molecular weights were introduced to avoid cracks or blisters during the process. Further more, the compatibilities of PEG/PVB and PEG/PMMA were studied. The results showed that PEG and PMMA exhibited better compatibility, with the feedstock more homogeneous and sintered ceramic parts higher strength.

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