Nutrient toxicity in pancreatic beta-cell dysfunction

Nutrients, such as glucose and fatty acids, have a dual effect on pancreati c beta-cell function. Acute administration of high glucose concentrations t o pancreatic beta-cells stimulates insulin secretion. In addition, short te rm exposure of this cell type to dietary fatty acids potentiates glucose-in duced insulin release. On the other hand, long-term exposure to these nutri ents causes impaired insulin secretion, characterized by elevated exocytosi s at low concentrations of glucose and no response when glucose increases i n the extracellular medium. In addition, other phenotypic changes are obser ved in these conditions. One major step in linking these phenotypic changes to the diabetic pathology has been the recognition of both glucose and fat ty acids as key modulators of beta-cell gene expression. This could explain the adaptative response of the cell to sustained nutrient concentration. O nce this phase is exhausted, the beta-cell becomes progressively unresponsi ve to glucose and this alteration is accompanied by the irreversible induct ion of apoptotic programs. The aim of this review is to present actual data concerning the development of the toxcity to the main nutrients glucose an d fatty acids in the pancreatic beta-cell and to find a possible link to th e development of type 2 diabetes.