Investigating b-cell Mass Dynamics with a Mass Balance Model
Wednesday, February 17, 1999 - 11:00am - 12:00pm
Diane Finegood (Simon Fraser University)
The mass of b-cells in the endocrine pancreas is an important determinant of insulin secretion and therefore glucose homeostasis. The mass of b-cells increases during growth and development and has been shown to change in response to changes in demand for insulin. The pathways which affect the b-cell mass include replication of pre-existing b-cells, differentiation of precursor cells (neogenesis), differentiation of other cell types (transdifferentiation) and cell death (apoptosis and necrosis). We described the quantitative relationship between these fluxes in the form of a b-cell mass balance equation (Diabetes 44:249-256, 1995). Through application of the mass balance model to data obtained from the literature, we detected for the first time a wave of b-cell death in the neonatal rat pancreas. Subsequent investigations have demonstrated that cell death during the wave is via apoptosis (programmed cell death), that it occurs in diabetes prone and diabetes resistant animals, and may play a role in initiation of the b-cell directed autoimmunity which leads to Type 1 diabetes mellitus. This b-cell mass balance model has also been useful for investigation of the dynamic response to fuel oversupply (glucose infusion) and the development of Type 2 diabetes in the Zucker Diabetic Fatty rat.