RESUMEN
20(R)-ginsenoside Rh2 (Rh2) is one of the most active components of red ginseng, possessing the beneficial effects in cancer prevention and metabolic diseases. However, the detailed mechanisms that contribute to Rh2-mediated bone formation remain largely unknown. In this study, we assessed the expression of 17 long non-coding RNAs (lncRNAs) in cultured MC3T3-E1 cells under Rh2 treatments. We found that lncRNA H19 was significantly increased in Rh2-treated MC3T3-E1 cells. Expression of lncRNA H19 was promoted in a dose- and time-dependent manner after Rh2 treatments. Increased expression of lncRNA H19 resulted in osteopontin (OPN) overexpression in Rh2-treated MC3T3-E1 cells. Furthermore, knockdown of lncRNA H19 by specific siRNAs significantly abolished the Rh2-mediated cell proliferation effects. Knockdown of lncRNA H19 also decreased both mRNA and protein levels of OPN in the Rh2-treated cells, which was accomplished by inhibiting histones H3 and H4 acetylation of OPN promoter. Importantly, OPN knockdown fully blocked Rh2 induced MC3T3-E1 cell proliferation. Our results suggest that lncRNA H19 is an important contributor to Rh2-mediated MC3T3-E1 proliferation by regulation of OPN.
Asunto(s)
Ginsenósidos/farmacología , Histonas/genética , Osteoblastos/efectos de los fármacos , Osteogénesis/efectos de los fármacos , Osteopontina/genética , ARN Largo no Codificante/genética , Acetilación/efectos de los fármacos , Animales , Línea Celular , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Regulación de la Expresión Génica , Histonas/metabolismo , Ratones , Osteoblastos/citología , Osteoblastos/metabolismo , Osteogénesis/genética , Osteopontina/metabolismo , Regiones Promotoras Genéticas , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , ARN Largo no Codificante/antagonistas & inhibidores , ARN Largo no Codificante/metabolismo , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/metabolismo , Transducción de SeñalRESUMEN
Physical activity improves well-being and reduces the risk of heart disease, cancer and type 2 diabetes mellitus in the general population. In individuals with established type 2 diabetes, physical activity improves glucose and lipid levels, reduces weight and improves insulin resistance. In type 1 diabetes mellitus, however, the benefits of physical activity are less clear. There is poor evidence for a beneficial effect of physical activity on glycaemic control and microvascular complications, and significant risk of harm through hypoglycaemia. Here we review the literature relating to physical activity and health in type 1 diabetes. We examine its effect on a number of outcomes, including glycaemic control, lipids, blood pressure, diabetic complications, well-being and overall mortality. We conclude that whilst there is sufficient evidence to recommend physical activity in the management of type 1 diabetes, it is still unclear as to what form, duration and intensity should be recommended and whether there is benefit for many of the outcomes examined.
Asunto(s)
Diabetes Mellitus Tipo 1/terapia , Promoción de la Salud , Actividad Motora , Adolescente , Adulto , Animales , Niño , Diabetes Mellitus Tipo 1/complicaciones , Medicina Basada en la Evidencia , Ejercicio Físico , HumanosRESUMEN
Type 1 diabetes is recognised to include an element of insulin resistance. Insulin resistance is an independent risk factor for the development of macro- and microvascular complications of Type 1 diabetes and may also contribute to the development of the disease. This understanding comes at a time when the incidence of Type 1 diabetes appears to be rising and the public health burden from its vascular complications is high. A variety of safe and efficacious manoeuvres are available to redress insulin resistance in Type 2 diabetes. So far however, clinical trials addressing insulin resistance in Type 1 diabetes have been small with only short periods of follow-up. Regardless, these trials have yielded promising results. This review examines the evidence for insulin resistance in the pathophysiology of Type 1 diabetes and its complications, the problems associated with its measurement, and summarizes the trials aimed at reducing insulin resistance in Type 1 diabetes. This includes a meta-analysis of controlled trials of adjuvant metformin in Type 1 diabetes.