19 research outputs found

    Insulinotropic compounds decrease endothelial cell survival

    No full text
    Hyperglycemia induces damage of vascular endothelial cells leading to diabetic complications. We investigated the effects of insulinotropic compounds and elevated glucose on endothelial cells in the absence or presence of vascular endothelial growth factor (VEGF). Human umbilical vein endothelial cells (HUVECs) were treated with glibenclamide, repaglinide and insulinotropic imidazolines at high glucose concentration in the presence or absence of VEGF and viability, proliferation and nitric oxide production were measured. Hyperglycemia inhibited pro-survival effects of VEGF on endothelial cells. Glibenclamide and repaglinide decreased HUVEC viability at elevated glucose concentration in the absence but not in the presence of VEGF, without affecting HUVEC proliferation. Repaglinide also had some positive influence on HUVEC function elevating NO production in the presence of VEGF. Imidazolines showed different activities on endothelial cell survival. Efaroxan diminished HUVEC viability at elevated glucose concentration in the presence, however not in the absence of VEGF, while RX871024 decreased HUVEC survival regardless of the presence of VEGF. Our data demonstrate an important interplay between the actual insulinotropic compounds, VEGF and ambient glucose concentration affecting the survival of the vascular endothelial cells. Consequently, this interplay needs to be taken into consideration when designing novel oral antidiabetic compounds. •Oral insulinotropic compounds decrease endothelial cell survival.•Sulfonylurea, glinide and imidazolines differently affect endothelial cell survival.•Repaglinide has some positive effect on endothelial function elevating NO production

    The imidazoline compound RX871024 promotes insulinoma cell death independent of AMP-activated protein kinase inhibition

    No full text
    We have previously shown that the insulinotropic imidazoline compound RX871024 induces death of insulinoma MIN6 cells, an effect involving stimulation of c-Jun N-terminal kinase (JNK) and caspase 3. It has also been reported that AMP-activated protein kinase (AMPK) activates JNK and induces β-cell death. Here we show that RX871024, but not another insulinotropic imidazoline compound (BL11282), suppressed AMPK activity in MIN6 cells. The inhibitory effect of RX871024 on AMPK was supported by the observation that the imidazoline induced lipid droplet formation in the cytoplasm of MIN6 cells. This reflects stimulation of anabolic pathways and inhibition of catabolic pathways in the cell that happen under conditions when AMPK is inhibited. Activation of AMPK by 5-aminoimidazole-4-carboxamide riboside (AICAR) elevated basal and cytokine-induced death in primary β-cells and in insulinoma MIN6 cells. RX871024 aggravated AICAR-induced insulinoma MIN6 cell death regardless of the presence of pro-inflammatory cytokines. The specific cytotoxic effect of imidazoline compound RX871024 on insulinoma cell death but not primary β-cell death is independent of its action on AMPK and may suggest the possibility of using this type of compound in the treatment of insulinomas

    The impact of new production technologies on the efficiency of agricultural enterprises

    No full text
    The article discusses the directions that contribute to improving the development efficiency of flour-milling enterprises, taking into account the effectiveness of the product marketing system via general scientific methods and theories of studying socio-economic phenomena and processes: logical, dialectical, systemic, technological, process and situational approaches. It has been shown that the diversification of production is an effective direction for the development of flour milling enterprises. In conclusion, to solve the priority tasks of product quality management in the aspect of ensuring sustainable effective development of the flour-milling industry, it is necessary to improve the equipment and technology of grain processing.El artículo discute las direcciones que contribuyen a mejorar la eficiencia del desarrollo de las empresas de molienda de harina, teniendo en cuenta la efectividad del sistema de comercialización de productos a través de métodos y teorías científicas generales de estudio de fenómenos y procesos socioeconómicos: lógico, dialéctico, sistémico, tecnológico , procesos y enfoques situacionales. Se ha demostrado que la diversificación de la producción es una dirección efectiva para el desarrollo de empresas de molienda de harina. En conclusión, para resolver las tareas prioritarias de gestión de la calidad del producto en el aspecto de garantizar un desarrollo eficaz y sostenible de la industria de molienda de harina, es necesario mejorar el equipo y la tecnología del procesamiento de granos
    corecore