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


CONCLUSIONS
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.
Laboratoire de Physiopathologie de la Nutrition, Université Paris Diderot, CNRS UMR 7059, Paris, France. meliskaraca@gmail.com
Melis
M
Karaca
Julien
J
Castel
Cécile
C
Tourrel-Cuzin
Manuel
M
Brun
Anne
A
Géant
Mathilde
M
Dubois
Sandra
S
Catesson
Marianne
M
Rodriguez
Serge
S
Luquet
Pierre
P
Cattan
Brian
B
Lockhart
Jochen
J
Lang
Alain
A
Ktorza
Christophe
C
Magnan
Catherine
C
Kargar
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D005434:Flow Cytometry; D005947:Glucose / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism*; D007930:Leucine / Q000494:pharmacology; D008297:Male; D018613:Microscopy, Confocal; D039842:Neural Cell Adhesion Molecule L1 / Q000378:metabolism*; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012794:Sialic Acids / Q000378:metabolism*
D007328:Insulin; D039842:Neural Cell Adhesion Molecule L1; D012794:Sialic Acids; C103469:polysialyl neural cell adhesion molecule; D011189:Potassium Chloride; D000255:Adenosine Triphosphate; D001120:Arginine; D000242:Cyclic AMP; D007930:Leucine; D005947:Glucose; D002118:Calcium