Trends in Endocrinology & Metabolism
ReviewLife and Death of the Pancreatic β Cells
Section snippets
Life History of the Endocrine Pancreas
Shortly before birth, replication becomes the major mechanism for adding new β cells to the pancreas, but both neogenesis (the differentiation process) and replication continue throughout adult life. In data from different-aged Sprague-Dawley rats, it was clear that β-cell mass increased with age in the adult rat6. Recently, two other studies have extended these findings. Data from mouse studies showed that, while male mice of the same age and same strain differed in body weight, their β-cell
Postnatal Origin of New β Cells
Islet neogenesis, while clearly the main pathway of β-cell increase during early–mid gestation, still occurs in the normal postnatal animal6., 9. and can be enhanced experimentally17., 19., 20., 21., 22., 23., 24., 25.. In the first few days after birth, many new islets are formed, and a second wave of neogenesis occurs about the time that weaning occurs14. In some experimental situations, new lobes of pancreas (exocrine and endocrine) are added26. Similarly, in retired breeders (six-months
Death or Survival?
The mechanisms of autoimmune destruction of β cells were reviewed recently32 and so will not be discussed here. Mathematical modeling of the β-cell mass predicted a normal turnover of β cells6. The physiological occurrence of β-cell apoptosis has been shown in vivo during the involution of the β-cell mass in the post partum pancreas14 and in a remodeling of the endocrine pancreas in the neonatal rat10. In the neonatal period, the simultaneous high levels of apoptosis and replication of β cells
Replacement of β Cells: Stem Cells and Precursor Cells
The possibility of unlimited sources of new β cells has sparked interest in determining the stem or precursor cells in the pancreas. The demonstration that bone marrow-derived stem cells can differentiate into hepatic cells47 has expanded our concept of what is possible. One exciting study introduced antibiotic resistance under the control of the insulin promoter and was able to select insulin-secreting cells from expanded mouse embryonic stem cells48. These cells had near-normal insulin
Acknowledgements
This work was supported by grants from the National Institutes of Health and the Juvenile Diabetes Foundation.
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