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91.
Glucagon-like Peptide-1 (GLP-1) and the Control of Glucose Metabolism in Mammals and Teleost Fish 总被引:4,自引:0,他引:4
Glucose metabolism in mammalian species and teleost fish iscontrolled by different metabolic pathways. These include differencesin the function of several major hormones, especially insulinand GLP-1. The major physiological role of GLP-1 in mammalsis to connect the consumption of nutrients with glucose metabolism.The glucose lowering effects of GLP-1 in the postprandial stateof mammals are regulated predominantly through metabolic pathwaysthat integrate different physiological processes. These are:(i) stimulation of insulin release from the pancreatic ß-cellduring hyperglycemia and (ii) inhibition of nutrient absorptionin the gastrointestinal tract. These effects are mediated bya same type of a highly selective GLP-1 receptor, often referredto as the "pancreatic GLP-1 receptor." In teleost fish GLP-1increases glucose levels through the activation of glycogenolysisand gluconeogenesis from liver. Functional characterizationof the recombinant GLP-1 receptor from zebrafish, which is thefirst example of a recombinant fish GLP-1 receptor, demonstratedthat zebrafish GLP-1 receptor has a binding specificity towardsa wider range of GLP-1 structures than the mammalian GLP-1 receptor.This property of the zebrafish GLP-1 receptor, and most likelyother fish GLP-1 receptors, sets apart the structure of thezebrafish GLP-1 receptor from the structures of mammalian GLP-1receptors. These differences in the binding specificity betweenthe zebrafish and mammalian GLP-1 receptors might reflect inpart the differences in the mechanism by which GLP-1 regulatesglucose metabolism in mammals and teleost fish. 相似文献
92.
Andrei Ogrel Alexei Ogrel Svetlana Ogrel Vitaliy Shvets Jan Raap 《International journal of peptide research and therapeutics》1998,5(2-3):175-178
Summary Synthesis of zervamicin IIB, specifically labeled at the α-position of glutamine-11 with15N, was achieved by the Fmoc/tert.-butyl strategy in solution using a fragment condensation approach. Three fragments of zervamicin IIB were obtained by stepwise
elongation with Fmoc amino acids using BOP as a coupling reagent. For the introduction of the highly sterically hindered α-aminoisobutyric
acid residues, BOP/DMAP activation was applied. Peptide fragments were coupled by means of the coupling reagent, CF3-PyBOP. Using the strategy developed, zervamicin IIB specifically15N labeled has been synthesized in 30% overall yield based on the isotopically labeled amino acid. From 600 MHz NMR spectroscopy
the position of the15N-label was clearly detected. The isotope enrichment (98 ±2%) was determined by FAB-mass spectrometry. 相似文献
93.
Valery Kukharenko Svetlana Sheleg Mikhail Freudine Elena Pichugina Alexander Delvig 《Human genetics》1994,94(1):80-82
Synthesis of glycosaminoglycans (GAGS) by fibroblasts derived from seven patients with Down's syndrome, five patients with Edwards' syndrome, and two patients with Patau's syndrome were studied in cell culture. The aneuploid strains were compared with diploid fibroblasts from age-matched controls. In terms of hyaluronic acid and sulfated GAG synthesis, the amount of synthesized hyaluronic acid was not significantly different between postnatal aneuploid strains and controls. 相似文献
94.
Zora Vradyov Svetlana Kiidayov Peter Siroka Duan Jal
《Animal Feed Science and Technology》2008,144(1-2):44-54
The objective of this study was to investigate effects of oil supplements on the composition of fatty acids (FA), especially of trans11-C18:1 (vaccenic acid, TVA) and cis9, trans11-C18:2 conjugated linoleic acid (c9,t11-CLA), in bacterial (BF) and protozoal (PF) fractions of rumen fluid of sheep that was fractionated centrifugation. Four sheep were fed a diet consisting of meadow hay (960 g dry matter (DM)/day) and of barley grain (240 g DM/day), with sunflower oil (SO), rapeseed oil (RO) or linseed oil (LO) as supplements (60 g/day) in a Latin square design. The oils were used as they are rich in linoleic acid (SO, 533 g/kg of FA), oleic acid (RO, 605 g/kg of FA) and α-linolenic acid (LO, 504 g/kg of FA). Compared to the control (i.e., without oils), oil supplements influenced the concentration of unsaturated (UFA) and saturated fatty acids (SFA). In both BF and PF, the main fatty acids were palmitic and stearic, but PF contained a higher proportion of TVA and c9,t11-CLA than BF. In PF, TVA concentrations, ranked by oil supplement, were SO > RO > LO > Control (174, 150, 118, 74 g/kg of FA, respectively) and the c9,t11-CLA concentrations were RO > SO > LO > Control (59, 51, 27 and 15 g/kg of FA, respectively). Concentrations of c9,t11-CLA in PF were two to three times higher than in BF with all the oil supplements versus the control. Oil treatments impacted the c9,t11-CLA concentration in the fractions, especially SO and RO. The protozoal fraction contained a higher proportion of TVA and c9,t11-CLA than did the bacterial fraction, and dietary addition of SO, RO and LO resulted in a higher incorporation of TVA into both bacterial and protozoal microbial fractions, which probably positively affected TVA flow from the rumen. 相似文献
95.
Svetlana V. Shilova Grigory M. Mirgaleev Ksenia A. Romanova Yury G. Galyametdinov 《Biopolymers》2023,114(10):e23555
This work reports synthesis of pH-responsive alginate/chitosan hydrogel spheres with the average diameter of 2.0 ± 0.05 mm, which contain cefotaxime that is an antibiotic of the cefalosporine group. The spheres provided the cefotaxime encapsulation efficiency of 95 ± 1%. An in vitro release of cefotaxime from the spheres in the media that simulate human biological fluids in peroral delivery conditions was found to be a pH-dependent process. The analysis of cefotaxime release kinetics by the Korsmeyer–Peppas model revealed a non-Fickian mechanism of its diffusion, which may be related to intermolecular interactions occurring between the antibiotic and chitosan. Conductometry, UV spectroscopy, and IR spectroscopy were used to study complexation of chitosan with cefotaxime in aqueous media with varied pH, characterize the composition of the complexes, and calculate their stability constants. The composition of the cefotaxime–chitosan complexes was found to correspond to the 1.0:4.0 and 1.0:2.0 molar ratios of the components at pH 2.0 and 5.6, respectively. Quantum chemical modeling was used to evaluate energy characteristics of chitosan–cefotaxime complexation considering the influence of a solvent. 相似文献
96.
Jason P. Holland Albert Kang Susan Cohrs Svetlana V. Selivanova Selena Milicevic Sephton Thomas Betzel Daniel Frey Mara Wieser Rolf Jaussi Richard A. Kammerer Roger Schibli Eliane Fischer 《化学与生物多样性》2013,10(4):538-555
Kinesin spindle protein (KSP), an ATP‐dependent motor protein, plays an essential role in bipolar spindle formation during the mitotic phase (M phase) of the normal cell cycle. KSP has emerged as a novel target for antimitotic anticancer drug development. In this work, we synthesized a range of new biphenyl compounds and investigated their properties in vitro as potential antimitotic agents targeting KSP expression. Antiproliferation (MTT (=3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl‐2H‐tetrazolium bromide)) assays, combined with fluorescence‐assisted cell sorting (FACS) and Western blot studies analyzing cell‐cycle arrest confirmed the mechanism and potency of these biphenyl compounds in a range of human cancer cell lines. Structural variants revealed that functionalization of biphenyl compounds with bulky aliphatic or aromatic groups led to a loss of activity. However, replacement of the urea group with a thiourea led to an increase in antiproliferative activity in selected cell lines. Further studies using confocal fluorescence microscopy confirmed that the most potent biphenyl derivative identified thus far, compound 7 , exerts its pharmacologic effect specifically in the M phase and induces monoaster formation. These studies confirm that chemical scope remains for improving the potency and treatment efficacy of antimitotic KSP inhibition in this class of biphenyl compounds. 相似文献
97.
F. William Sunderman Alison H. Varghese Olga S. Kroftova Svetlana Grbacivankovic Jaromir Kotyza Arun K. Datta Milton Davis Wojciech Bal Kazimierz S. Kasprzak 《Molecular reproduction and development》1996,44(4):507-524
A Ni(II)-binding serpin, pNiXA, is abundant in Xenopus oocytes and embryos. Kinetic assays show that purified pNiXa strongly inhibits bovine α-chymotrypsin (K1 = 3 mM), weakly inhibits porcine elastase (K1 = 0.5 μM), and does not inhibit bovine trypsin. The reversible, slow-binding inhibition of α-chymotrypsin by pNiXa is unaffected by Ni(II). Ovochymase in egg exudates is inhibited by pNiXa, but to a limited extent, even at high pNiXa concentrations. An octadecapeptide that models the His-rich domain (-HRHRHEQQGHHDSAKHGH-) of pNiXa forms six-coordinate, octahedral Ni(II)-complexes when the N-terminus is acetylated, and a square-planar Ni(II)-complex when the N-terminus is unblocked. Spectroscopy reveals two distinct types of octahedral Ni(II)-coordination to the N-acetylated octadecapeptide, involving, respectively, 3–4 and 5–6 imidazole nitrogens; the octadecapeptide undergoes partial, reversible precipitation in pH-and Ni(II)-dependent fashion, suggesting an insoluble, Ni(II)-coupled (Hx)n-dimer. Such (Hx)n-peptide interaction is confirmed by an enzyme-linked biotin-avidin assay with N-biotin-KHRHRHE-amide and N-acetyl-KHRHRHE-resin beads, which become coupled after adding Ni(II) or Zn(II). H2O2 oxidation of 2′-deoxyguanosine to mutagenic 8-hydroxy-2′deoxyguanosine is enhanced by the octahedral Ni(II)-octadecapeptide complex, although the effect is more intense with the square-planar Ni(II) octadecapeptide complex. Immunoperoxidase staining of whole mounts wish pNiXa antibody shows that pNiXa is distributed throughout gastrula-stage embryos and is localized during organogenesis in the brain, eye, spinal cord, myotomes, craniofacial tissues, and other sites of Ni(II) induced anomalies. Patterns of pNiXa staining are similar in controls and Ni(II)-exposed embryos. Binding of Ni(II) to pNiXa may cause embryotoxicity by enhancing oxidative reactions that produce tissue injury and genotoxicity. Although the natural target proteinases for pNiXa inhibition have not been established, pNiXa may be an important regulator of proteolysis during embryonic development. © 1996 Wiley-Liss, Inc. 相似文献
98.
Grabeklis Andrey R. Skalny Anatoly V. Skalnaya Anastasia A. Zhegalova Irina V. Notova Svetlana V. Mazaletskaya Anna L. Skalnaya Margarita G. Tinkov Alexey A. 《Biological trace element research》2019,187(1):230-242
Biological Trace Element Research - Chronic exposure to lead causes disruption to energy production mechanisms and tissue damage, in particular through its binding to thiol groups and competition... 相似文献
99.
Nicholas Mikolajewicz Simon Sehayek Paul W. Wiseman Svetlana V. Komarova 《Biophysical journal》2019,116(10):2009-2022
The skeleton constantly interacts and adapts to the physical world. We have previously reported that physiologically relevant mechanical forces lead to small repairable membrane injuries in bone-forming osteoblasts, resulting in release of ATP and stimulation of purinergic (P2) calcium responses in neighboring cells. The goal of this study was to develop a theoretical model describing injury-related ATP and ADP release, their extracellular diffusion and degradation, and purinergic responses in neighboring cells. After validation using experimental data for intracellular free calcium elevations, ATP, and vesicular release after mechanical stimulation of a single osteoblast, the model was scaled to a tissue-level injury to investigate how purinergic signaling communicates information about injuries with varying geometries. We found that total ATP released, peak extracellular ATP concentration, and the ADP-mediated signaling component contributed complementary information regarding the mechanical stimulation event. The total amount of ATP released governed spatial factors, such as the maximal distance from the injury at which purinergic responses were stimulated. The peak ATP concentration reflected the severity of an individual cell injury, allowing to discriminate between minor and severe injuries that released similar amounts of ATP because of differences in injury repair, and determined temporal aspects of the response, such as signal propagation velocity. ADP-mediated signaling became relevant only in larger tissue-level injuries, conveying information about the distance to the injury site and its geometry. Thus, we identified specific features of extracellular ATP and ADP spatiotemporal signals that depend on tissue mechanoresilience and encode the severity, scope, and proximity of the mechanical stimulus. 相似文献
100.
Deng L Vysotski ES Markova SV Liu ZJ Lee J Rose J Wang BC 《Protein science : a publication of the Protein Society》2005,14(3):663-675
The crystal structures of calcium-loaded apo-aequorin and apo-obelin have been determined at resolutions 1.7A and 2.2 A, respectively. A calcium ion is observed in each of the three EF-hand loops that have the canonical calcium-binding sequence, and each is coordinated in the characteristic pentagonal bipyramidal configuration. The calcium-loaded apo-protein retain the same compact scaffold and overall fold as the unreacted photoproteins containing the bound substrate, 2-hyroperoxycoelenterazine, and also the same as the Ca2+-discharged obelin bound with product, coleneteramide. Nevertheless, there are easily discerned shifts in both helix and loop regions, and the shifts are not the same between the two proteins. It is suggested that these photoproteins to sense Ca2+ concentration transients and to produce their bioluminescence response on the millisecond timescale. A mechanism of intrastructural transmission of the calcium signal is proposed. 相似文献