High glucose concentration in T1D patients modulates apoptotic protein expression: Down regulation of BAX and FAS and up regulation of XIAP

Type 1 diabetes mellitus (T1D) is an autoimmune disease characterized by a progressive destruction of pancreatic β cells. It has been reported that patients with autoimmune diseases exhibit decreased expression of caspase 3 and other pro-apoptotic markers in peripheral blood mononuclear cells (PBMC).AimTo estimate the expression of apoptosis markers in PBMC from T1D patients cultured with high glucose concentration.ResultsAt 11 mM of glucose, the pro-apoptotic gene fas showed a 7-fold decreased expression in the T1D group compared to controls, while bax showed a 50-fold decreased expression (medians 0.14 and 0.02, respectively, considering patients as 1). At 44 mM of glucose, there is a decreased expression of the same genes, but less abrupt (medians 0.75 and 0.47). Only the anti-apoptotic gene xiap showed a 2-fold increased expression at 11 mM of glucose (median 2.3). Regarding the clinical history, no relationships were observed with age of diagnosis, ketoacidosis, glucose at debut or GAD-65 and IA-2 titles.ConclusionWe can conclude that the apoptotic mechanisms in PBMC of T1D patients under high glucose conditions are altered, and this is proved by the decreased expression of the pro-apoptotic genes fas and bax and by the increased expression of the anti-apoptotic gene xiap.