For the purposes of this article, glucose toxicity of the islet is defined as nonphysiological and potentially irreversible β-cell damage caused by chronic exposure to supraphysiological glucose concentrations. In its initial stages, this damage is characterized by defective insulin gene expression (1,2). Desensitization refers to a temporary physiological state of cellular refractoriness to glucose stimulation induced by repeated or prolonged exposure to high glucose concentrations.