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

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