RESUMEN
Ipragliflozin is a novel and selective sodium-glucose cotransporter 2 (SGLT2) inhibitor that induces sustained increases in urinary glucose excretion by inhibiting renal glucose reabsorption and thereby exerting a subsequent antihyperglycemic effect. Here, we examined the effect of ipragliflozin on body weight in high-fat diet-induced (HFD) obese rats. Treatment of ipragliflozin (10mg/kg once daily) reduced body weight despite a slight increase in food intake. Dual-energy X-ray absorptiometry and computed tomography demonstrated that the reduction in body weight was accompanied by reduced visceral and subcutaneous fat masses but not lean mass or bone mineral content. Analysis of plasma and urinary parameters suggested the possibility that ipragliflozin enhanced lipolysis and fatty acid oxidation, and indirect calorimetry showed that ipragliflozin decreased the heat production rate from glucose but increased the rate from fat and lowered the respiratory exchange ratio. In conclusion, these data demonstrate that ipragliflozin-induced urinary glucose excretion specifically reduces fat mass with steady calorie loss by promoting the use of fatty acids instead of glucose as an energy source in HFD rats. By improving hyperglycemia and promoting weight reduction, ipragliflozin may prove useful in treating type 2 diabetes in obese individuals.
Asunto(s)
Adiposidad/efectos de los fármacos , Fármacos Antiobesidad/farmacología , Dieta Alta en Grasa , Ácidos Grasos/metabolismo , Glucósidos/farmacología , Metabolismo de los Lípidos/efectos de los fármacos , Obesidad/tratamiento farmacológico , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Tiofenos/farmacología , Animales , Biomarcadores/sangre , Biomarcadores/orina , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Modelos Animales de Enfermedad , Metabolismo Energético/efectos de los fármacos , Glucosuria/metabolismo , Hipoglucemiantes/farmacología , Obesidad/etiología , Obesidad/metabolismo , Obesidad/fisiopatología , Oxidación-Reducción , Ratas , Transportador 2 de Sodio-Glucosa/metabolismo , Factores de Tiempo , Regulación hacia Arriba , Pérdida de Peso/efectos de los fármacosAsunto(s)
Antineoplásicos/uso terapéutico , Imidazoles/uso terapéutico , Proteínas Asociadas a Microtúbulos/antagonistas & inhibidores , Naftoquinonas/uso terapéutico , Animales , Diseño de Fármacos , Humanos , Proteínas Inhibidoras de la Apoptosis , Ratones , Survivin , Células Tumorales CultivadasRESUMEN
We discovered an epoch-making gene transfer method utilizing discharge plasma. Although an electroporation method is commonly used in present gene transfer experiments, it cannot transfer genes into primary cells sufficiently. The atmospheric pressure discharge plasma employed in this study was originally used for surface treatment of non-biological materials. We hypothesized that it could provide a suitable effect on the surface of target cells and applied it to gene transfer into various types of cells. The plasma technology succeeded in the efficient transfer of green fluorescence protein (GFP) plasmid into post-mitotic neuronal cells obtained from cerebral cortices of rats, into which an electroporation with conventional equipment cannot transfer genes sufficiently, as the cells were attached. After the transfection of rat pheochromocytoma PC12 cells with the GFP gene by plasma treatment, the cells retained their function, that is, nerve growth factor-induced differentiation. Furthermore, gene transfer with the plasma technology was also applicable to other types of cell lines such as HeLa cells and Chinese hamster lung (CHL) cells as adherent cell lines, and Jurkat cells as a suspended cell line, and another type of primary cell, human umbilical vein endothelial cells (HUVEC). In conclusion, the plasma method is an epoch-making gene transfer technology which efficiently transfers genes into primary cells into which electroporation cannot transfer genes. Moreover, the method is able to universally transfer genes into various types of cells as the function of the cells was maintained.