In vivo functional heterogeneity among β-cells.

Abstract

The concept of functional heterogeneity among β-cells proposes that each cell differs in its sensitivity to glucose and is recruited in a glucose-dependent manner into both biosynthetic and secretory active states in order to adapt insulin secretion to the metabolic environment. Therefore, characterization of β-cell populations with different metabolic sensitivities would lead to the development of new therapeutic strategies. Based on heterogeneous surface PSA-NCAM expression on β-cells, we have recently characterized two groups of cells, namely β(high) and β(low)-cells, in rat. Differences in insulin secretory capacity and in gene expression profiles suggest that β(low)-cells are immature and/or non-functional cells in contrast to highly glucose responsive fully functional β(high)-cells. Moreover, the relative distribution of β(high) and β(low)-cells correlated with physiological and pathological states regarding the functional β-cell mass. Here we summarize our main results on β(high) and β(low)-cell populations and discuss some of the open remaining questions.