Abstract

The growth and development of the endocrine pancreas has been studied for many years, but questions remain concerning the regulation of the mass of insulin-producing β-cells both in the normal growing pancreas and during the pathogenesis of diabetes. The homeostatic control of β-cell mass in both normal and pathophysiological conditions is based on the balance of cell proliferation, cell growth, and cell death. To gain insight into the relative contribution of each of these dynamic processes, we first mathematically analyzed the data available on the components involved in the maintenance of β-cell mass, including rates of replication, β-cell volume, and the β-cell mass itself, at various ages in normal Sprague-Dawley rats. Then these data were combined in a simple mass balance equation to construct a mathematical model of the dynamics of the β-cell mass in the normal growing rat pancreas. Such a model has allowed us to infer the contributions of fluxes that cannot be measured, i.e., neogenesis and cell death, to the known mass of β-cells. Another important contribution of this model is to raise unanswered questions concerning the control of the balance of cell death and cell renewal in the endocrine pancreas.