Figure 4.

The proposed model of the role of MT1 in the pathogenesis of type 2 diabetes. Under physiological conditions requiring the stimulation of insulin secretion, Mt1 gene expression is repressed, thereby allowing enhanced secretory response to meet the metabolic needs. In contrast, under diabetes conditions, the unfavorable diabetic environment and subsequent induction of oxidative stress and other stress pathways lead to the upregulation of Mt1 gene expression. The latter is a double-edged sword that will, on one hand, counter beta-cell stress, at least in part through scavenging of ROS, and on the other hand, inhibit GSIS. These events occur sequentially during the natural history of diabetes, as depicted in the insert. In the prediabetic phase (beta-cell compensation), the beta-cell function is markedly enhanced in parallel with significant downregulation of MT gene expression. Conversely, in the diabetic phase (beta-cell decompensation), beta-cell function declines in parallel with significant upregulation of MT gene expression. GSIS: glucose-stimulated insulin secretion.