Nutrient toxicity in pancreatic β-cell dysfunctionToxicidad de nutrientes en la disfunción de la célula beta pancreática

Nutrients, such as glucose and fatty acids, have a dual effect on pancreatic β-cell function. Acute administration of high glucose concentrations to pancreatic β-cells stimulates insulin secretion. In addition, short term exposure of this cell type to dietary fatty acids potentiates glucose-induced insulin release. On the other hand, long-term exposure to these nutrients causes impaired insulin secretion, characterized by elevated exocytosis at low concentrations of glucose and no response when glucose increases in the extracellular medium. In addition, other phenotypic changes are observed in these conditions. One major step in linking these phenotypic changes to the diabetic pathology has been the recognition of both glucose and fatty acids as key modulators of β-cell gene expression. This could explain the adaptative response of the cell to sustained nutrient concentration. Once this phase is exhausted, the β-cell becomes progressively unresponsive to glucose and this alteration is accompanied by the irreversible induction of apoptotic programs. The aim of this review is to present actual data concerning the development of the toxicity to the main nutrients glucose and fatty acids in the pancreatic β-cell and to find a possible link to the development of type 2 diabetes.