Regenerating islets can be induced by the administration of poly(ADP-ribose) synthetase inhibitors to 90% depancreatized rats. In screening a regenerating islet-derived cDNA library, we previously isolated a novel gene. reg (regenerating gene), which encodes a 165-amino acid protein with a 21-amino acid signal sequence. In the present study, we have examined the expression and localization of reg protein in the regenerating islets by immunocytochemical techniques using a monoclonal antibody against a recombinant rat reg protein of 144 amino acids without the signal sequence. Light microscopy examination showed strong immunoreactivity for reg protein in the regenerating islets of the rats at two weeks and two months after 90% pancreatectomy, whereas reg protein was almost undetectable in normal rat islets or in the islets of the rats one year after the pancreatectomy. Almost all the reg protein-positive cells were stained for insulin. By applying the immunogold technique at the ultrastructural level, it was demonstrated that both reg protein and insulin occur in the central granular core of the regenerating Beta cell secretory granules. These results suggest that reg protein is synthesized in and secreted from the regenerating Beta cells and that its expression is closely associated with Beta-cell regeneration.

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Ah&actConditioned media of human glial cell lines induced alkaline phosphatase activity in cultured calf artery endothelial cells. The maximal alkaline phosphatase activity in the culture was comparable to the level in isolated brain capillary endothelial cells. An induction factor in the conditioned media was purified and identified as interleukind from its amino-terminal sequence, molecular weight, amino acid composition and immunoreactivity. Recombinant interleukin-6 had similar induction activity. Our findings raise the possibility that interleukin-6 induces and modulates alkaline phosphatase activity in endothelial cells during normal development of the blood-brain barrier and under certain pathological conditions.