The role of endoplasmic reticulum stress induced by glucosamine in pancreatic beta cells dysfunction

The endoplasmic reticulum (ER) represents the cellular compartment where newly synthesized proteins acquire their correct folding. Many factors can interfere during this process, leading to the accumulation of misfolded proteins into the ER. Such ER dysfunction is collectively termed "ER stress". To survive under ER stress conditions, cells activate a self-protective mechanism, termed the unfolded protein response (UPR). The ER dysfunction plays an important role in various diseases including Type 2 diabetes (T2D). It has been reported that hyperglycaemia (HG) causes the progressive deterioration of beta cells through a mechanism called glucose toxicity and that ER stress may be involved in the consequent pancreatic beta cell dysfunction. Glucosamine (GlcN), generated by the hexosamine pathway (HP) during HG, induces ER stress and causes disturbances similar to glucose toxicity. In this study, we evaluate the role of ER stress induced by GlcN in cultured beta cells (INS-1E) and in isolated pancreatic mouse islets.