VMP1- Related autophagy induced by fructose rich diet in β-cells: its prevention by incretins

• Autores: Maiztegui, Bárbara; Boggio, Verónica; Roman, Carolina Lisi; Flores, Luis Emilio; Del Zotto, Héctor Herminio; Ropolo, Alejandro; Grasso, Daniel Horacio; Vaccaro, María I.; Gagliardino, Juan José
• Año de publicación: 2017
• Idioma: inglés
• Tipo de recurso: artículo
• Materia: Bioquímica; incretins; fructose-induced β-cell-injury; autophagy; β-cell mass; β-cell function
• Institución: Universidad Nacional de La Plata

To demonstrate the role of autophagy and incretins on fructose‐induced alteration in β‐cell mass and function. Methods: Normal Wistar rats were fed (3 weeks) with commercial diet without (C) or with 10% fructose in drinking water (F) alone or plus sitagliptin (CS and FS) or exendin‐4 (CE and FE). Serum levels of metabolic/endocrine parameters, β‐cell mass, morphology/ultrastructure and apoptosis, VMP1 expression and glucose‐stimulated insulin secretion (GSIS) were studied. Complementary, islets isolated from normal rats were cultured (3 days) without (C) or with F and F plus exendin‐4 (FE) or chloroquine (FCQ). Expression of autophagy related‐proteins (VMP1 and LC3), apoptotic/antiapoptotic markers (caspase‐3 and Bcl‐2), GSIS and insulin mRNA levels were measured. Results: F rats developed impaired glucose tolerance (IGT) and a significant increase in plasma triglyceride, TBARS, insulin levels, HOMAIR and HOMA‐β indexes. Significant β‐cell mass reduction was associated to an increased apoptotic rate and morphological/ultrastructural changes indicative of autophagic activity. All these changes were prevented by either sitagliptin or exendin‐4. In cultured islets, F significantly enhanced insulin mRNA and GSIS, decreased Bcl‐2 mRNA levels and increased caspase‐3 expression. Chloroquine reduced these changes suggesting autophagy participation in this process. Indeed, F induced the increase of both, VMP1 expression and LC3‐II, suggesting that VMP1‐related autophagy is activated in injured β‐cell. Exendin‐4 prevented islet‐cell damage and autophagy development. Conclusions: VMP1‐related autophagy is a reactive process against Finduced islet dysfunction, being prevented by exendin‐4 treatment. This knowledge could help to use autophagy as potential target for preventing progression from IGT toT2DM.
Centro de Endocrinología Experimental y Aplicada (CENEXA)
Facultad de Ciencias Médicas (FCM)