RESUMEN
Previous work has revealed that Cx36, the sole connexin expressed in the insulin-producing beta cells, enhances the secretion of insulin, and promotes the resistance of beta cells against pro-inflammatory cytokines. In parallel, the anti-diabetic sulphonylurea glibenclamide was shown to promote the assembly and function of Cx36 channels. Here, we assessed whether glibenclamide could protect the insulin-producing cells against conditions mimicking those expected at the onset of type 1 diabetes. We found that the drug 1) protected in vitro the mouse MIN6 cells from the apoptosis and loss of Cx36, which are induced by Th1 cytokines; 2) prevented the development of hyperglycemia as well as the loss of beta cells and Cx36, which rapidly develop with aging in untreated NOD mice; 3) modified the proportion of effector CD4+ and CD8+ T cells in pancreatic draining lymph nodes. The data imply that an early glibenclamide treatment may help protecting beta cells against the autoimmune attack, which triggers the development of type 1 diabetes.
Asunto(s)
Diabetes Mellitus Tipo 1/prevención & control , Gliburida/farmacología , Hipoglucemiantes/farmacología , Células Secretoras de Insulina/efectos de los fármacos , Insulinoma/prevención & control , Animales , Células Cultivadas , Citocinas/metabolismo , Diabetes Mellitus Tipo 1/inmunología , Diabetes Mellitus Tipo 1/metabolismo , Femenino , Células Secretoras de Insulina/inmunología , Células Secretoras de Insulina/metabolismo , Insulinoma/inmunología , Insulinoma/metabolismo , Ratones , Ratones Endogámicos NODRESUMEN
The mucosal lining forms the physical and chemical barrier that protects against pathogens and hostile particles and harbors its own population of bacteria, fungi and archea, known as the microbiota. The immune system controls tolerance of this population of microorganisms that have proven to be beneficial for its host. Keeping its physical integrity and a correct balance with the microbiota, the mucosa preserves its homeostasis and its protective function and maintains host's health. However, in some conditions, pathogens may succeed in breaching mucosal homeostasis and successfully infecting the host. In this review we will discuss the role the mucosa plays in the defense against bacterial pathogens by considering the gap junction protein connexins. We will detail their implication in mucosal homeostasis and upon infection with bacteria in the respiratory and the gastrointestinal tracts.