Gryllus bimaculatus extract protects against palmitate-induced beta-cell death by inhibiting ceramide synthesis

Abstract

Type I diabetes mellitus is an autoimmune disease characterized by the destruction of beta-cells, leading to severe insulin deficiency. Environmental factors and genetic predisposition are implicated in beta-cell destruction, which is the final step in a cascade of complex events. Possible triggers of beta-cell destruction are activation of Fas, activation of perforin, increased generation of reactive oxygen species, increased production of inflammatory cytokines, and endoplasmic reticulum (ER) stress. In this study, we examined whether Gryllus bimaculatus (GB) extract could prevent palmitate-induced beta-cell apoptosis. Exposure to GB extract prevented palmitate-induced death of MIN6 cells, a mouse pancreatic beta-cell line. Palmitate increased total ceramide levels with the elevation of ceramide synthase (CerS)1, CerS4, and CerS6 expressions. Treatment with GB extract decreased the levels and expressions of ceramides related to insulin resistance. CerS4 and CerS6 overexpression, but not CerS1 overexpression, increased palmitate-induced MIN6 cell death by increasing ceramide synthesis. Oppositely, inhibition of ceramide synthesis by fumonisin B1 treatment partially recovered palmitate-induced MIN6 cell death. Furthermore, GB extract reduced ER stress (phosphorylation of PERK and elF2a), NF-kappa B-iNOS signaling, and the phosphorylation of MAP kinase (JNK, p38). GB extract reduced proapoptotic Bax protein expression but increased anti-apoptotic Bcl2 expression. In addition, CerS4 and CerS6 overexpression aggravated impairment of insulin secretion by palmitate, but GB extract recovered it. In conclusion, GB could be a functional food that improves palmitate-induced beta-cell death and insulin secretion.