Exploring Functional β-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. 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

Matching and naming objects by shape or function: Age and context effects in preschool children.

Three experiments tested preschoolers' use of abstract principles to classify and label objects by shape or function. Three- and 4-year-olds were instructed to match objects by shape or function. Four-year-olds readily adopted either rule, but 3-year-olds followed only the shape rule. Without a rule, 4-year-olds tended to match by shape unless object function was shown during matching (Experiment 2). Three-year-olds' ability to use a function rule was tested in several conditions (re-presenting functions; reminders to "use the rule"; repeating rule on every trial). None induced consistent function matching (Experiment 3). Supplemental memory and verbal tasks showed that 3-year-olds have trouble using function as an abstract basis of comparison. Naming data, however, show that preschoolers are learning that object labels are based on function. The results show preschoolers' growing flexibility in adopting abstract generalization rules and growing knowledge of conventions for extending words