15th WMS World Congress on Targeting Mitochondria

Introduction. Regulation of blood glucose level by insulin secretion is the main function of pancreatic beta cells, which could be easily affected by oxidative stresses during onset of Type-2 diabetes (T2DM). Advanced glycated end products (AGEs), formed by non-enzymatic Maillard reaction or polyol pathway flux, have direct implicats on the oxidative stress development of diabetes related complications (1). The aim of this study was to examine the possible effects of AGE-products Nε-(carboxymethyl)-lysine (CML) and Nε-(carboxyethyl)-lysine (CEL) and the amadori product fructosyl-lysine (FL) on beta cells' viability and function in vitro.  Methods. In this study, the human beta cell line, 1.1B4, was cultured and treated with CML, CEL and FL at the doses sustaining %80 cell viability in vitro. Results. The expression of pro-inflammatuary cytokins, IL-2 and IL-6, was induced by CML, CEL and FL. The insulin and C-peptite levels secreted in response to low (5 uM) and high glucose (25,5 uM) media showed that the insulin stimulation  Discussion. Although CML and CEL are also adverse effective on mitochondrial dysfunction, the amadori product FL strongly alters mitochondrial functions and distrubs energy metabolism causing to shift to glycolysis. Consequently, the insulin synthesis capacity was dropped in beta cells with decreased insulin secretion level from beta cells.