Pancreatic-derived factor (PANDER) is an islet-specific cytokine present in both pancreatic ␣-and ␤-cells, which, in vitro, induces ␤-cell apoptosis of primary islet and cell lines. In this study, we investigated whether PANDER is secreted by pancreatic ␣-and ␤-cells and whether PANDER secretion is regulated by glucose and other insulin secretagogues. In mouse-derived insulin-secreting ␤-TC3 cells, PANDER secretion in the presence of stimulatory concentrations of glucose was 2.8 ؎ 0.4-fold higher (P < 0.05) than without glucose. Insulin secretion was similarly increased by glucose in the same cells. The total concentration of secreted PANDER in the medium was ϳ6 -10 ng/ml [IFN]-␥) play vital roles in ␤-cell dysfunction and death and in the development of type 1 diabetes (2-6). Recently, it was shown that glucose causes islet ␤-cells to produce IL-1␤, while the released IL-1␤ has a deleterious effect on human pancreatic islets (7,8). These studies suggest that production and release of cytokines from pancreatic islet cells are involved in ␤-cell dysfunction and death in hyperglycemia. To date, although several cytokines have been shown to be involved in ␤-cell dysfunction and death, the precise mechanisms of type 1 diabetes are still incompletely understood, suggesting that other potential factors may be involved.Pancreatic-derived factor (PANDER), also known as FAM3B (9,10), is one of four members of a new cytokine family recently identified using the algorithm ostensible recognition of folds (11) while searching for novel cytokines based on their predicted secondary structure. The rationale for this approach is that the secondary structure of cytokines is highly conserved through evolution. Many cytokines, such as IL

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