Pdx1 and other factors that regulate pancreatic β‐cell survival

A progressive reduction in β‐cell mass occurs in the evolution of diabetes. Thus understanding the mechanisms responsible for this reduction in β‐cell mass is important for understanding the pathogenesis of diabetes and in developing novel approaches to prevention and treatment. Pancreatic duodenal homeobox 1 (Pdx1) is a transcription factor that plays a central role in pancreatic β‐cell function and survival. Complete deficiency of Pdx1 is associated with pancreatic agenesis, and partial deficiency leads to severe β‐cell dysfunction, and increases β‐cell death and diabetes both in rodent and human. Chronic hyperglycaemia and dyslipidaemia, which are major features of type 2 diabetes, cause β‐cell dysfunction via reduced Pdx1 expression. Inhibition of insulin/insulin‐like growth factor (Igf) signalling followed by reduced Pdx1 expression is a common pathway induced by the majority of the mechanisms in apoptotic β‐cells. Although the report so far paid little attention to non‐apoptotic β‐cell death (autophagy and necrosis), we expect these are also involved in the pathogenesis of diabetes. The potential role of Pdx1 in non‐apoptotic β‐cell death should also be considered in future studies in diabetes, and in attempts to develop novel agents that target this process for prevention and treatment of the disorder.