Developmentally Regulated Expression of Survivin in Human Pancreatic Islets

Abstract

Islet cell apoptosis plays a role in both normal development of the endocrine pancreas and in the pathogenesis of Type I and Type II diabetes. The molecular mechanisms regulating islet cell death and survival in both normal and pathological situations are still not completely elucidated. The inhibitor of apoptosis protein (IAP) Survivin has an anti-apoptotic function mediated by several mechanisms; these include inhibiting caspase 3 and caspase 7. Survivin expression has been reported in human fetal islets and it may play a role in pancreatic remodeling and islet homeostasis. However, there are no data concerning either its expression in neonate or adult islets or its expression in any specific subtype of islet cells. We identified Survivin expression by immunohistochemistry in alpha cells and beta islet cells of 5/5 fetal pancreases. In contrast, fetal delta cells failed to demonstrate any detectable level of Survivin expression. Survivin expression was subsequently lost in the beta cells but not the alpha cells of 5/5 newborns and 5/5 adult subjects. Neonatal and adult delta cells maintained the lack of Survivin expression seen in fetal islets. These data show that different subtypes of islet cells differ in their pattern of Survivin expression. Furthermore, expression of Survivin in the beta cells is developmentally regulated.