Abstract / Summary
PDX-1 and MafA are insulin gene transcription factors and maintain mature pancreatic β-cell function. After chronic exposure to hyperglycemia, however, the expression levels of PDX-1 and MafA are substantially suppressed by provoked oxidative stress and the activation of the JNK/c-Jun pathway, which further aggravates β-cell function. In addition, glucocorticoids are often used to treat a variety of diseases, but they often induce hyperglycemia, not only by increasing insulin resistance, but also by directly impairing insulin biosynthesis in β-cells. Glucocorticoids bind and activate the glucocorticoid receptor in β-cells, while PDX-1 and MafA expression levels are substantially suppressed through the activation of the JNK/c-Jun pathway, which could explain the molecular mechanism behind glucocorticoid-induced β-cell dysfunction. There are similarities in the molecular mechanism for β-cell dysfunction induced by chronic hyperglycemia and glucocorticoid administration. On the other hand, a GLP-1 receptor agonist rapidly enhances microvascular flow in pancreatic islets in a NO-dependent manner. Such phenomena show that the islet microenvironment is substantially regulated by GLP-1 receptor signaling. Also, based on these data, it is likely that rapid microvascular adaptation contributes to the maintenance of β-cell function under diabetic conditions.