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- Title
Pdx1 and other factors that regulate pancreatic β-cell survival.
- Authors
Fujimoto, K.; Polonsky, K. S.
- Abstract
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.
- Subjects
TREATMENT of diabetes; GROWTH factors; CELL death; INSULIN; TYPE 2 diabetes
- Publication
Diabetes, Obesity & Metabolism, 2009, Vol 11, p30
- ISSN
1462-8902
- Publication type
Article
- DOI
10.1111/j.1463-1326.2009.01121.x