To clarify the relationship between variations in beta-cell mass and pancreatic function, we investigated the possibility to analyze, quantify, and sort beta-cell subpopulations with different functional maturity. To this aim, we tested the reliability of the sialylated form of neural cell adhesion molecule (NCAM) (PSA-NCAM) as a marker of beta-cell functional activity. Islet cells isolated from adult rats were analyzed for their PSA-NCAM abundance using an anti-PSA-NCAM antibody. We found that PSA-NCAM is expressed only in beta-cells. The PSA-NCAM labeling was also studied with a fluorescence-activated cell sorter. We showed that the beta-cell population is heterogeneous for PSA-NCAM labeling. To directly determine the relationship between PSA-NCAM labeling and beta-cell activity, in vitro insulin secretion studies were performed on sorted beta-cell subpopulations using a perifusion technique. Two beta-cell subpopulations were analyzed: one that was highly labeled for PSA-NCAM and another that was poorly labeled. Insulin secretion from high PSA-NCAM-labeled beta-cells was significantly higher than that in low PSA-NCAM-labeled beta-cells. This differential expression in the beta-cell population was well correlated with differences in glucose responsiveness. PSA-NCAM seems thus suitable for use as a tool to identify beta-cell subpopulations according to their glucose responsiveness.

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