Exploring Functional β-Cell Heterogeneity In Vivo Using PSA-NCAM as a Specific Marker

BACKGROUND: The mass of pancreatic β-cells varies according to increases in insulin demand. It is hypothesized that functionally heterogeneous β-cell subpopulations take part in this process. Here we characterized two functionally distinct groups of β-cells and investigated their physiological relevance in increased insulin demand conditions in rats. METHODS: Two rat β-cell populations were sorted by FACS according to their PSA-NCAM surface expression, i.e. β(high) and β(low)-cells. Insulin release, Ca(2+) movements, ATP and cAMP contents in response to various secretagogues were analyzed. Gene expression profiles and exocytosis machinery were also investigated. In a second part, β(high) and β(low)-cell distribution and functionality were investigated in animal models with decreased or increased β-cell function: the Zucker Diabetic Fatty rat and the 48 h glucose-infused rat. RESULTS: We show that β-cells are heterogeneous for PSA-NCAM in rat pancreas. Unlike β(low)-cells, β(high)-cells express functional β-cell markers and are highly responsive to various insulin secretagogues. Whereas β(low)-cells represent the main population in diabetic pancreas, an increase in β(high)-cells is associated with gain of function that follows sustained glucose overload. CONCLUSION: Our data show that a functional heterogeneity of β-cells, assessed by PSA-NCAM surface expression, exists in vivo. These findings pinpoint new target populations involved in endocrine pancreas plasticity and in β-cell defects in type 2 diabetes.