RESUMEN
According to several population-based studies, betel nut chewing is associated with metabolic syndrome and diabetes in British South Asians and Taiwanese. However, the underlying molecular mechanism is not yet clear. Arecoline is an alkaloid-type natural product found in betel nuts. Our aim was to clarify the influence of betel nut extract and arecoline on lipid accumulation and insulin signaling in adipocytes. We found that betel nut extract and arecoline blocked lipid storage in 3T3-L1 adipocytes. The possible mechanism may function by inhibiting the expression of the insulin receptor, glucose transporter-4, fatty acid synthase, and the lipid droplet proteins perilipin and adipophilin. In addition, betel nut extract and arecoline increased the basal level of IRS-1 serine(307) phosphorylation and decreased insulin-stimulated IRS-1 tyrosine, Akt, and PI3 kinase phosphorylation. In conclusion, betel nut extract and arecoline have diabetogenic potential on adipocytes that may result in insulin resistance and diabetes at least in part via the obstruction of insulin signaling and the blockage of lipid storage.
Asunto(s)
Adipocitos/efectos de los fármacos , Areca/efectos adversos , Arecolina/efectos adversos , Diabetes Mellitus Tipo 2/metabolismo , Expresión Génica/efectos de los fármacos , Insulina/metabolismo , Transducción de Señal/efectos de los fármacos , Células 3T3-L1 , Adipocitos/metabolismo , Adipocitos/patología , Animales , Areca/química , Proteínas Portadoras/antagonistas & inhibidores , Proteínas Portadoras/genética , Proteínas Portadoras/metabolismo , Diabetes Mellitus Tipo 2/patología , Ácido Graso Sintasas/antagonistas & inhibidores , Ácido Graso Sintasas/genética , Ácido Graso Sintasas/metabolismo , Glucosa/metabolismo , Transportador de Glucosa de Tipo 4/antagonistas & inhibidores , Transportador de Glucosa de Tipo 4/genética , Transportador de Glucosa de Tipo 4/metabolismo , Proteínas Sustrato del Receptor de Insulina/antagonistas & inhibidores , Proteínas Sustrato del Receptor de Insulina/genética , Proteínas Sustrato del Receptor de Insulina/metabolismo , Resistencia a la Insulina , Metabolismo de los Lípidos/efectos de los fármacos , Metabolismo de los Lípidos/genética , Proteínas de la Membrana/antagonistas & inhibidores , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Ratones , Perilipina-1 , Perilipina-2 , Fosfatidilinositol 3-Quinasas/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Fosfoproteínas/antagonistas & inhibidores , Fosfoproteínas/genética , Fosfoproteínas/metabolismo , Fosforilación , Extractos Vegetales/efectos adversos , Extractos Vegetales/química , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismoRESUMEN
Helium-neon laser (He-Ne Laser, 632.8 nm) is a low-energy laser that has therapeutic efficacy on various clinical conditions. Our previous study has demonstrated efficacy of He-Ne laser on vitiligo, a disease characterized by skin depigmentation. To regain skin tone on vitiligo lesions, the process began by the migration of the immature melanoblasts (MBs) to the epidermis, which was followed by their functional development to produce melanin. In this study, we investigated the physiologic effects of He-Ne laser irradiation on two MB cell lines: the immature NCCmelb4 and the more differentiated NCCmelan5. The intricate interactions between MBs with their innate extracelluar matrix, fibronectin, were also addressed. Our results showed that He-Ne laser irradiation enhanced NCCmelb4 mobility via enhanced phosphorylated focal adhesion kinase expression and promoted melanogenesis in NCCmelan5. In addition, He-Ne laser decreased the affinity between NCCmelb4 and fibronectin, whereas the attachment of NCCmelan5 to fibronectin increased. The alpha5beta1 integrin expression on NCCmelb4 cells was enhanced by He-Ne laser. In conclusion, we have demonstrated that He-Ne laser induced different physiologic changes on MBs at different maturation stages and recapitulated the early events during vitiligo repigmentation process brought upon by He-Ne laser in vitro.