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

Figure 1 Typical progress of type 2 diabetes. The development of type 2 diabetes is associated with pancreatic β-cell dysfunction and insulin resistance. First, overeating and/or obesity lead to the development of insulin resistance and normal β-cells secrete a larger amount of insulin to compensate for the increased insulin resistance. Next, large adipocytes secrete a larger amount of free fatty acids and/or various inflammatory cytokines which gradually deteriorate β-cell function and finally lead to the onset of diabetes. This process is known as “β-cell lipotoxicity”. Once hyperglycemia becomes apparent, β-cell function progressively deteriorates; insulin biosynthesis and secretion are reduced. This process is known as “β-cell glucose toxicity” which is often observed in type 2 diabetes.