Up-regulation of the expression of activins in the pancreatic duct by reduction of the beta-cell mass.

Activins expressed in progenitor cells of the pancreas regulate differentiation of endocrine cells during development. Neogenesis of beta-cells takes place in adult animals under some conditions, and beta-cells are thought to arise from precursors locating in the pancreatic duct. In the present study, we investigated whether or not activins are expressed in the duct where beta-cell neogenesis is initiated. mRNA for the beta(A)- and beta(B)-subunits was expressed in isolated mouse pancreatic ducts. Immunohistochemically, the beta(A)-subunit was detected in the pancreatic duct and colocalized with cytokeratin, a marker of ductal cells. The beta(A)-subunit was also expressed in nestin-positive cells in the duct. Likewise, the beta(B)-subunit was detected in the pancreatic duct. In addition, mRNA for the type II and type IIB activin receptors was expressed in the duct. Expression of mRNA for two activin subunits was markedly increased after streptozotocin injection. Similarly, the mRNA expression was up-regulated after partial pancreatectomy. These results indicate that activins are expressed in the pancreatic duct and are up-regulated shortly after the reduction of the beta-cell mass. Induction of activins in the duct may be a critical step in the initiation of beta-cell neogenesis.