Changes in metabolic demands dynamically regulate the total mass of adult pancreatic ␤-cells to adjust insulin secretion and preserve glucose homeostasis. Glucose itself is a major regulator of ␤-cell proliferation by inducing insulin secretion and activating ␤-cell insulin receptors. Here, we show that islet cell autoantigen 512 (ICA512)/IA-2, an intrinsic tyrosine phosphatase-like protein of the secretory granules, activates a complementary pathway for ␤-cell proliferation. On granule exocytosis, the ICA512 cytoplasmic domain is cleaved and the resulting cytosolic fragment (ICA512-CCF) moves into the nucleus where it enhances the levels of phosphorylated STAT5 and STAT3, thereby inducing insulin gene transcription and granule biogenesis. We now show that knockdown of ICA512 decreases cyclin D1 levels and proliferation of insulinoma INS-1 cells, whereas ␤-cell regeneration is reduced in partially pancreatectomized ICA512 ؊/؊ mice. Conversely, overexpression of ICA512-CCF increases both cyclin D1 and D2 levels and INS-1 cell proliferation. Up-regulation of cyclin D1 and D2 by ICA512-CCF is affected by knockdown of STAT3 and STAT5, respectively, whereas it does not require insulin signaling. These results identify ICA512 as a regulator of cyclins D and ␤-cell proliferation through STATs and may have implication for diabetes therapy.diabetes ͉ insulin ͉ phosphatase ͉ regeneration ͉ secretion

An important question in the legal context is how suggested statements about fictitious events develop over a course of various interviews. Sixty-seven first-graders were interviewed four times about one real and one fictitious event, applying various suggestive techniques. A fifth, nonsuggestive, interview was conducted by blind experts. Over the course of the interviews there was a considerable increase in assents to the fictitious events. Moreover, few significant differences in criteria-based content analysis-criteria were revealed between true and fictitious statements in the fifth interview. Accordingly, experts had difficulties in discriminating between true and suggested accounts. Furthermore, several children were convinced of the truth of their reports, even after having been partially debriefed in a sixth interview. Implications for statement validity assessment are discussed.

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