Review
Life and Death of the Pancreatic β Cells

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Abstract

Pancreatic β cells are responsible for maintaining the body's glucose levels within a very narrow range; their population is dynamic, with compensatory changes to maintain euglycemia. Throughout the lifetime of a mammal, low levels of β-cell replication and apoptosis are balanced and result in a slowly increasing mass of β cells. The emphasis in this review is on recent insights on the natural history of the β cell in a normal pancreas: sources of renewal, survival and changes in differentiation.

Section snippets

radical dot 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

radical dot 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

radical dot 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

radical dot 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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