9 research outputs found

    Procyanidin effects on an impaired glucose metabolism: a further insight into procyanidin signalling in adipose cells

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    CATALÀ A un extracte de procianidines de pinyol de raïm (GSPE) se l'hi han atribuït efectes mimètics d'algun dels efectes fisiològics de la insulina, però alhora la seva acció mostra algunes divergències respecte la pròpia hormona. Aquest fet suggereix un possible interès d'aquestes procianidines en patologies vinculades amb la resistència a la insulina. Per aquest motiu, l'objectiu principal d'aquesta tesi és entendre com les procianidines de la dieta modulen el metabolisme de la glucosa, principalment a teixit adipós i sota una condició de resistència a insulina. Els resultats obtinguts mostren que 30 dies de tractament amb 25 mg GSPE/Kg PC milloren la situació de resistència a insulina provocada per una dieta de cafeteria i evidencien que el teixit adipós és una clara diana per GSPE. En cèl·lules en cultiu s'observa com GSPE activa el receptor de la insulina i proteïnes de la via de senyalització de la insulina de manera diferent a la pròpia hormona. L'estudi es completa demostrant que les estructures oligomèriques de GSPE poden reproduir els efectes fins ara atribuïts a les procianidines.ANGLÈS A grape-seed derived procyanidins extract (GSPE) was reported to mimic some of the physiological effects of insulin. However, GSPE showed some divergences when compared to insulin action, which suggests that procyanidins could be useful on a state of impaired insulin action. Therefore, the main purpose of this thesis was to understand how dietary procyanidins modulate glucose metabolism, mainly in adipose tissue and under an insulin resistant condition.Results show that a treatment of 25 mg GSPE/Kg bw for 30 days on cafeteria-diet-fed rats has a positive effect in improving some insulin resistance parameters and that white adipose tissue is also a clear target for procyanidins. Cell culture studies showed the ability of procyanidins for activating the insulin receptor and its ability for activating proteins kinases involved in the insulin signalling pathway. The GSPE study was completed showing that oligomeric structures of GSPE can reproduce the total GSPE effects

    Distinct control of MyD88 adapter-dependent and Akt kinase-regulated responses by the interleukin (IL)-1RI co-receptor, TILRR

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    Inflammatory responses are controlled through members of the interleukin-1 receptor (IL-1R)/Toll-like receptor superfamily. Our earlier work demonstrates that the IL-1 receptor type 1 (IL-1RI) co-receptor, Toll-like and IL-1 receptor regulator (TILRR), amplifies IL-1 activation of NF-?B and inflammatory genes. Here we show that TILRR similarly promotes IL-1-induced anti-apoptotic signals and reduces caspase-3 activity. Further, the TILRR-induced effects on cell survival and inflammatory responses are controlled through distinct parts of the IL-1RI regulatory Toll IL-1 receptor (TIR) domain. Alanine-scanning mutagenesis identified a functional TILRR mutant (R425A), which blocked increases in cell survival and upstream activation of Akt but had no effect on amplification of MyD88- dependent inflammatory responses. A second mutant (D448A) blocked TILRR potentiation of MyD88-dependent signals and inflammatory activation but had no impact on cell survival. Secondary structure predictions suggested that the mutations induce distinct alterations in the a-helical structure of the TILRR core protein. The results indicate a role for TILRR in selective amplification of NF-?B responses through IL-1RI and suggest that the specificity is determined by changes in receptor conformation and adapter protein recruitment

    Early embryonic exposure of freshwater gastropods to pharmaceutical 5-alpha-reductase inhibitors results in a surprising open-coiled "banana-shaped" shell

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    In vertebrates, the steroidogenesis enzyme 5α-reductase converts testosterone to the more potent androgen 5α-dihydrotestosterone. Homologues of 5α-reductase genes have been identified in molluscs. However, recent findings suggest that vertebrate-type steroid androgens are not utilised in molluscan reproductive development. Genomic searches have revealed that molluscs do not possess many of the steroidogenic enzymes required to make testosterone, nor a nuclear androgen receptor. Consequently, the role of 5α-reductase in molluscs presents a mystery. Here, developmental exposures of Biomphalaria glabrata to selective pharmaceutical 5α-reductase inhibitors elicited a strong, highly reproducible phenotypic response characterised by the development of elongated "banana-shaped" shell morphology. In comparison to untreated snails, the shells are open-coiled and the whorls are unattached. Dutasteride (5α-reductase inhibitor) is approximately 10-times more potent at provoking the banana-shaped shell phenotype than finasteride, paralleling the pharmaceuticals' efficacy in humans. Other enzyme inhibitors with different modes of action were tested to investigate the specificity of the phenotype. However, only the pharmaceutical 5α-reductase inhibitors provoked the response. Dutasteride elicited the same phenotype in a second gastropod, Physella acuta. In the absence of evidence for de novo androgen steroidogenesis in molluscs, these findings suggest that novel substrates for 5α-reductase exist in gastropods, lending support to the contention that molluscan endocrinology differs from the well-characterised vertebrate endocrine system.</p
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