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Int. microbiol ; 22(4): 461-470, dic. 2019. graf, tab
Artigo em Inglês | IBECS | ID: ibc-185064


To date, tripartite tricarboxylate transport (TTT) systems are not well characterized in most organisms. To investigate which carbon sources are transported by the TTT system of A. mimigardefordensis DPN7T, single deletion mutants were generated lacking either completely both sets of genes encoding for these transport systems tctABCDE1 and tctABDE2 in the organism or the two genes encoding for the regulatory components of the third chosen TTT system, tctDE3. Deletion of tctABCDE1 (MIM_c39170-MIM_c39210) in Advenella mimigardefordensis strain DPN7T led to inhibition of growth of the cells with citrate indicating that TctABCDE1 is the transport system for the uptake of citrate. Because of the negative phenotype, it was concluded that this deletion cannot be substituted by other transporters encoded in the genome of strain DPN7T. A triple deletion mutant of A. mimigardefordensis lacking both complete TTT transport systems and the regulatory components of the third chosen system (ΔTctABCDE1 ΔTctABDE2 ΔTctDE3) showed a leaky growth with alpha-ketoglutarate in comparison with the wild type. The other investigated TTT (TctABDE3, MIM_c17190-MIM_c17220) is most probably involved in the transport of alpha-ketoglutarate. Additionally, thermoshift assays with TctC1 (MIM_c39190) showed a significant shift in the melting temperature of the protein in the presence of citrate whereas no shift occurred with alpha-ketoglutarate. A dissociation constant Kd for citrate of 41.7 μM was determined. Furthermore, alternative alpha-ketoglutarate transport was investigated via in silico analysis

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Ácidos Tricarboxílicos/metabolismo , Bordetella/genética , Betaproteobacteria/enzimologia , Propionatos/metabolismo , Succinato-CoA Ligases/metabolismo , Transportadores de Ácidos Dicarboxílicos/genética , Ácidos Dicarboxílicos/metabolismo , Espectrometria de Massas/métodos , Ciclo do Ácido Cítrico , Betaproteobacteria/classificação , Propionatos/química , Succinato-CoA Ligases/genética
J. physiol. biochem ; 71(1): 29-42, mar. 2015. ilus
Artigo em Inglês | IBECS | ID: ibc-133900


High-fat diet (HFD) elevates circulatory fatty acids and influences glucose and fat metabolism.Azelaic acid (AzA), a naturally occurring alpha,ω-dicarboxylic acid in wheat, rye, barley, oat seeds and sorghum, has been reported to exert antidiabetic effects in HFD-induced type 2 diabetes mellitus (T2DM) C57BL/6J mice. The present study was undertaken to identify the genes that are differentially modulated by treatment with AzA in HFD-fed mice. Mice were fed HFD for 10 weeks and subjected to intragastric administration of 80 mg/kg body weight (BW) of AzA daily along with HFD from 11 to 15 weeks. Lipid profile, adipokines and cytokines were examined in the plasma/liver of mice. Whole genome profiling was performed in the liver of mice using microarray and validated by qRT-PCR, Western blot and immunohistochemical analyses. HFD intake resulted in significantly elevated lipids (except high-density lipoproteins), resistin, tumour necrosis factor alpha and interleukin-6 with marked reduction in adiponectin. Administration of AzA to HFD-fed mice significantly restored the lipids, adipokines and cytokines to near normal. Transcript profiling revealed that HFD intake activated the genes involved in stress response, cell cycle regulation and apoptosis. Treatment with AzA caused increased expression of genes involved in reactive oxygen species (ROS) scavenging, receptor-mediated signalling, transcription, protein modification and insulin signal transduction. AzA activates insulin signal molecules leading to insulin sensitivity. The ability of AzA to modulate the expression of these genes supports the notion that AzA is a promising drug candidate for the treatment of insulin resistance associated with T2DM (AU)

Ratos , Animais , Dieta Hiperlipídica , Ácidos Dicarboxílicos/farmacocinética , Diabetes Mellitus Tipo 2/fisiopatologia , Expressão Gênica , Genômica , Insulina/metabolismo , Transdução de Sinais/fisiologia
Endocrinol. nutr. (Ed. impr.) ; 53(4): 256-262, abr. 2006.
Artigo em Espanhol | IBECS | ID: ibc-043657


El GLP-1 (glucagon-like peptide-1) es una hormona con carácter de incretina que contribuye al control de la homeostasis de la glucosa, y que por su acción insulinotrópica, insulinotrófica y también insulinomimética, se está considerando para el tratamiento de la diabetes mellitus tipo 2. In vitro, el GLP-1 tiene efectos anabólicos sobre el metabolismo hepático de la glucosa en la rata normal y diabética, y sobre el del músculo y la grasa de la rata y del hombre; en el tejido adiposo, el GLP-1 es, además, lipolítico y lipogénico. En estos 3 tejidos extrapancreáticos, el GLP-1 parece actuar a través de receptores específicos, distintos en estructura y/o vía de señalización del pancreático, sobre los que se ha propuesto un inositolfosfoglicano como posible segundo mensajero. Por otro lado, la respuesta secretora de la célula ß al GLP-1, modulada en condiciones normales por la concentración extracelular de glucosa, está alterada en la diabetes tipo 2, debido, posiblemente, a la imposibilidad de la célula para reconocer a la hexosa; sin embargo, nutrientes no glucídicos, capaces de sortear los defectos específicos de reconocimiento de la célula ß diabética hacia la glucosa, como son los ésteres de ácidos dicarboxílicos, potencian y/o prolongan su acción insulinotrópica. Además, el GLP-1 no sólo ejerce un papel regulador de la ingestión de alimentos, induciendo sensación de saciedad, sino que también parece tener acciones beneficiosas en síndromes de carácter neurodegenerativo central y periférico. En cualquier caso, el valor del papel potencial terapéutico del GLP-1 no sólo en la diabetes sino también en la obesidad y en las enfermedades cardíacas y nerviosas, es un hecho que no se debe ignorar, cuyo mecanismo de acción concreto, no del todo conocido, requiere aclaración

Glucagon-like peptide-1 (GLP-1) is an incretin hormone that contributes to the control of glucose homeostasis. Because of its insulinotropic, insulinotrophic and insulinomimetic actions, it is being considered for the treatment of type 2 diabetes mellitus. In vitro, GLP-1 has anabolic effects on glucose metabolism in the liver of normal and diabetic rats and in rat and human skeletal muscle and fat; moreover, in fat tissue, GLP-1 is also lipolytic and lipogenic. In these three extrapancreatic tissues, GLP-1 seems to act through specific receptors, distinct in structure and/or signaling pathway from pancreatic one, for which an inositolphosphoglycan has been proposed as a possible second messenger. The secretory response of ß cells to GLP-1, modulated in normal conditions by the extracellular glucose concentration, is altered in type 2 diabetes mellitus, possibly due to the inability of the cell to recognize the hexose; however, non-glucose nutrients able to bypass the specific hexose recognition defects of the diabetic ß cell, such as dicarboxylic acid esters, potentiate and/or prolong the insulinotropic action of GLP-1. Moreover, GLP-1 not only plays a regulatory role in food intake, by inducing satiety, but also seems to have beneficial effects on central and peripheral neurodegenerative syndromes. The value of the potential therapeutic role of GLP-1, not only in diabetes but also in obesity and cardiac and central nervous system diseases, should not be ignored, and its mechanism of action, which is not clearly understood, requires elucidation

Ratos , Animais , Peptídeos/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Obesidade/tratamento farmacológico , Doença de Alzheimer/tratamento farmacológico , Ácidos Dicarboxílicos , Ilhotas Pancreáticas