PLoS ONE (Jan 2009)

Exploring functional beta-cell heterogeneity in vivo using PSA-NCAM as a specific marker.

  • Melis Karaca,
  • Julien Castel,
  • Cécile Tourrel-Cuzin,
  • Manuel Brun,
  • Anne Géant,
  • Mathilde Dubois,
  • Sandra Catesson,
  • Marianne Rodriguez,
  • Serge Luquet,
  • Pierre Cattan,
  • Brian Lockhart,
  • Jochen Lang,
  • Alain Ktorza,
  • Christophe Magnan,
  • Catherine Kargar

DOI
https://doi.org/10.1371/journal.pone.0005555
Journal volume & issue
Vol. 4, no. 5
p. e5555

Abstract

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BACKGROUND: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. METHODS: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. RESULTS: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. CONCLUSION: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.