Down-regulation of pancreatic transcription factors and incretin receptors in type 2 diabetes

Figure 2 Possible molecular mechanism for suppression of insulin biosynthesis in type 2 diabetes. Under diabetic conditions, hyperglycemia induces oxidative stress and thereby leads to suppression of insulin biosynthesis and secretion which is accompanied by reduction of nuclear pancreatic duodenal homeobox 1 (PDX-1) and MafA expression. Oxidative stress and subsequent activation of the JNK pathway translocate Foxo1 from cytoplasm to nuclei, leading to translocation of PDX-1 from nuclei to cytoplasm in β-cells. In addition, oxidative stress and subsequent induction of c-Jun expression suppress nuclear expression of MafA in β-cells. Therefore, it is likely that induction of oxidative stress and suppression of nuclear PDX-1 and MafA expression are involved in β-cell glucose toxicity found in type 2 diabetes.