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

Laboratoire de Physiopathologie de la Nutrition, Université Paris Diderot, CNRS UMR 7059, Paris, France.
PLoS ONE (Impact Factor: 3.23). 02/2009; 4(5):e5555. DOI: 10.1371/journal.pone.0005555
Source: PubMed


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

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    • "PSA-NCAM is not exclusively expressed in CNS. For instance, β high -and β low -pancreatic cells have been characterized based on differential PSA-NCAM expression (Karaca et al., 2009). In order to investigate the potential contamination of pancreatic endocrine cells among the PSA-NCAM + cells, we analyzed the gene expression profile of the PSA-NCAM positive fraction using whole genome micro array. "
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