Pancreatic development and adult diabetes

Low birth weight is an important risk factor for type 2 diabetes in later l ife. Maturity-onset diabetes of the young has been linked to genetic sequen ce abnormalities in transcription factors known to be involved in endocrine pancreatic development. These observations suggest that both the maternal environment and the fetal genome can influence the number and/or function o f pancreatic beta cells in early life, and that this has life-long implicat ions for postnatal diabetes. This article reviews the evidence that suggest s that beta cells derive from a neogenic process within the pancreatic duct al epithelium, controlled by specific transcription factors and locally act ing peptide growth factors. In rodents, many of the fetal phenotypes of bet a cells are destroyed during neonatal life in a developmental apoptosis and are replaced by a second wave of neogenesis. This results in islets with i nsulin release characteristics suited to postnatal life. The timing and amp litude of these ontological events are altered by nutritional sufficiency, and this may be mediated by changes in pancreatic growth factor expression, particularly of the IGF axis. Because beta-cell plasticity after the perin atal period is limited, a dysfunctional programming of beta-cell ontogeny m ay present a long-term risk factor for glucose intolerance and type 2 diabe tes. This critical window of pancreatic development is likely to occur in t hird trimester of human development.