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In recent years, a number of cross-talk systems have been identified which feed into the insulin signalling cascade at the level of insulin receptor substrate (IRS) tyrosine phosphorylation, e.g., receptor and non-receptor tyrosine kinases and G-protein-coupled receptors. At the molecular level, a number of negative modulator and feedback systems somehow interacting with the beta-subunit (catecholamine-, phorbolester-, or tumor necrosis factor-alpha-induced serine/threonine phosphorylation, carboxy-terminal trimming by a thiol-dependent protease, association of inhibitory/regulatory proteins such as RAD, PC1, PED, alpha2-HS-glycoprotein) have been identified as candidate mechanisms for the impairment of insulin receptor function by elevations in the activity and/or amount of the corresponding modification enzymes/inhibitors. Both decreased responsiveness and sensitivity of the insulin receptor beta-subunit for insulin-induced tyrosine autophosphorylation have been demonstrated in several cellular and animal models of metabolic insulin resistance as well as in the adipose tissue and skeletal muscle of diabetic patients and obese Pima Indians compared to non-obese subjects. Therefore, induction of the insulin signalling cascade by bypassing the defective insulin receptor kinase may be useful for the therapy of non-insulin dependent diabetes mellitus. During the past two decades, phosphoinositolglycans (PIGs) of various origin have been demonstrated to exert potent insulin-mimetic metabolic effects upon incubation with cultured or isolated muscle and adipose cells. However, it remained to be elucidated whether these compounds actually manage to trigger insulin signalling and if so at which level of hierarchy within the signalling cascade the site of interference is located. Recent studies using isolated rat adipocytes and chemically synthesized PIG compounds point to IRS1/3 tyrosine phosphorylation by p59Lyn kinase as the site of cross-talk, the negative regulation of which by interaction with caveolin is apparently abrogated by PIG. This putative mechanism is thus compatible with the recently formulated caveolin signalling hypothesis, the supporting data for which are reviewed here. Though we have not obtained experimental evidence for the involvement of PIG in physiological insulin action, the potential cross-talk between insulin and PIG signalling, including the caveolae/detergent-insoluble glycolipid-enriched rafts as the compartments where the corresponding signalling components are concentrated, thus represent novel targets for signal transduction therapy.  相似文献   

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Summary In vitro studies, using 2 separate techniques, have shown that the anti-inflammatory agent azapropazone caused displacement of warfarin from its plasma albumin binding and it is therefore suggested that such a displacement mechanism may be involved in the reported clinical interaction between these 2 drugs.  相似文献   

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Zusammenfassung Es wurde gezeigt, dass die Adsorption von Mycoplasmen an Ehrlich Ascites-Tumorzellen an das Vorhandensein von neuraminidase-empfindlichen Zellrezeptoren gebunden ist.  相似文献   

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森林凋落物与土壤质量的互作效应研究   总被引:11,自引:0,他引:11  
凋落物与土壤的相互关系研究是生态学领域的研究热点之一,其中凋落物质量对土壤质量的影响较大。本文阐述了凋落物质量对土壤质量的影响,从土壤生物学性质、理化性质等方面概述了土壤质量对凋落物分解所起的作用,并就凋落物和土壤的相互关系进行了评述,展望了该研究领域的发展趋势。  相似文献   

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Aldosterone injected i.m. decreased the release of renomedullary PGEs and the index (urinary Na/K ratio) in conscious normotensive intact and adrenalectomized rats. Coadministration of spironolactone increased the release of PGEs as well as the index (urinary Na/K ratio). The effect of spironolactone was partly inhibited by aspirin injected in a ratio 5:1 (aspirin:spironolactone), and effect which could be reversed by the infusion of a synthetic prostaglandin (PGA2) in a subhypotensive dose.  相似文献   

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Summary Aldosterone injected i.m. decreased the release of renomedullary PGEs and the index (urinary Na/K ratio) in conscious normotensive intact and adrenalectomized rats. Coadministration of spironolactone increased the release of PGEs as well as the index (urinary Na/K ratio). The effect of spironolactone was partly inhibited by aspirin injected in a ratio 51 (aspirin: spironolactone), an effect which could be reversed by the infusion of a synthetic prostaglandin (PGA2) in a subhypotensive dose.Acknowledgements. The authors gratefully acknowledge Dr J. Pike, Upjohn Company, Kalamazoo, Michigan, USA, who kindly provided prostaglandins used for this study. This work was supported by a grant from INSERM (ATP 32 76 64) to Dr N. Papanicolaou.  相似文献   

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Optomotor nystagmic activity has been elicited in the "encéphale isolé" cat during repetitive electric stimulation of selective oculomotor regions of the frontal cortex and superior colliculus. These regions were nystagmogenic only when facilitated by a cortical arousal or a vestibular activation.  相似文献   

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The receptor (CXCR4) for the stromal-derived factor-1 (SDF1) and the urokinase-receptor (uPAR) are up-regulated in various tumors. We show that CXCR4-transfected cells migrate toward SDF1 on collagen (CG) and do not on vitronectin (VN). Co-expression of cell-surface uPAR, which is a VN receptor, impairs SDF1-induced migration on CG and allows migration on VN. Blocking fMLP receptors (fMLP-R), alpha-v integrins or the uPAR region capable to interact with fMLP-Rs, impairs migration of uPAR/CXCR4-transfected cells on VN and restores their migration on CG. uPAR co-expression also reduces the adherence of CXCR4-expressing cells to various components of the extracellular matrix (ECM) and influences the partitioning of beta1 and alpha-v integrins to membrane lipid-rafts, affecting ECM-dependent signaling. uPAR interference in CXCR4 activity has been confirmed in cells from prostate carcinoma. Our results demonstrate that uPAR expression regulates the adhesive and migratory ability of CXCR4-expressing cells through a mechanism involving fMLP receptors and alpha-v integrins.  相似文献   

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Summary The sum of the neuraminidase activities found in the isolated soluble and particulate fractions of chick liver was considerably higher than that observed in the cytoplasmic extract from which these fractions were obtained. Addition of increasing amounts of particulate neuraminidase to a constant amount of the soluble preparation resulted in a progressive loss of enzyme activity.This investigation was supported in part by U. S. Public Health Service Grant NS09176 from the National Institutes of Health.  相似文献   

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Summary The effects of externally and internally applied bradykinin on the excitability of single myelinated nerve fibers were studied. External bradykinin (10 M) slightly prolongs the action potential of a single myelinated nerve fiber; hence, when the fibers are stimulated by long-lasting pulses, this raises the frequency of repetitive firing in sensory fibers and evokes repetitive activity in motor fibers. Under voltage-clamp conditions, sodium channel inactivation is slowed, while sodium channel activation remains unaffected. Prolonged depolarization of th membrane leads to a maintained sodium current. The voltage dependence of the steady-state sodium current inactivation (h ) is shifted in the depolarized direction by 10 mV. Internally applied bradykinin produces a frequency-dependent block of the sodium current. The phenomena described here imply that more than one site on the sodium channel is modified by bradykinin.  相似文献   

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Summary Interaction between the slow negative-positive waves of human evoked electrospinograms produced by descending and segmental volleys was tested under general anaesthesia. A partial occlusion was demonstrated in these slow waves.This work was supported in part by the Japanese Ministry of Education.  相似文献   

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The effects of externally and internally applied bradykinin on the excitability of single myelinated nerve fibers were studied. External bradykinin (10 microM) slightly prolongs the action potential of a single myelinated nerve fiber; hence, when the fibers are stimulated by long-lasting pulses, this raises the frequency of repetitive firing in sensory fibers and evokes repetitive activity in motor fibers. Under voltage-clamp conditions, sodium channel inactivation is slowed, while sodium channel activation remains unaffected. Prolonged depolarization of the membrane leads to a maintained sodium current. The voltage dependence of the steady-state sodium current inactivation (h infinity) is shifted in the depolarized direction by approximately 10 mV. Internally applied bradykinin produces a frequency-dependent block of the sodium current. The phenomena described here imply that more than one site on the sodium channel is modified by bradykinin.  相似文献   

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