Abstract

Regulation of pancreatic β-cell mass is an essential matter to understand pathophysiology of diabetes. Physiological and pathological changes of β-cell mass associated with aging, obesity and diabetes have been reported for over a century. However, the degree of compensation or alteration significantly varies among literature. The difficulty in studying the human pancreas is its large size and uneven distribution of β-cells/islets. Whole pancreas analysis has revealed intra-individual (regional) and inter-individual heterogeneity in β-cell mass, which hampers accurate quantification. Furthermore, physical β-cell loss is not the only contributing factor, but “dysfunctional” β-cells may be involved in insulin deficiency as well. Development of a practical stereological approach to quantify β-cell mass to overcome intra-individual and inter-individual heterogeneity would provide a standardized methodology in the field. Identification of marker(s) for quantifying dysfunctional β-cells that synthesize insulin but are deficient in insulin secretion should lead to a better understanding of β-cell pathophysiology.