Introduction

B-cells of the islets of Langerhans, the site of insulin production, have only a limited capacity for regeneration. In adult mouse and rat islets the population of replicating B-cells was estimated to be only about 1 % of total B-cells (Logothetopoulos, 1972). However, certain substances, such as glucose (Andersson, 1975), essential amino acids (Swenne et al., 1980), insulin (Rabinovitch et al., 1982), growth hormone (Rabinovitch et al., 1983) and epicatechin (Hii & Howell, 1984), were reported to stimulate some B-cell replication in fetal, newborn, or adult islets; nevertheless, the percentage of replicating B-cells was only about twice as high in B-cells treated with these substances than in control cells. Hyperplastic changes in the islets of Langerhans involving B-cells were observed in the pancreatic remnants of 90% depancreatized rats in the first few weeks after partial pancreatectomy, but thereafter extensive B-cell degeneration and degranulation were noticeable and the rats became severely diabetic (Martin & Lacy, 1963; Clark et al., 1982). This low capacity for regeneration in pancreatic B-cells creates a predisposition for the development of diabetes mellitus (Hellerström et al., 1976).

In 1984, Yonemura et al. demonstrated that administration of poly(ADP-ribose) synthetase inhibitors such as nicotinamide and 3- aminobenzamide to 90% depancreatized rats induces continuous regeneration of pancreatic B-cells, thereby preventing the development of diabetes in the partly depancreatized rats (Yonemura et al., 1984; Okamoto, 1985; Okamoto et al., 1985). Recently, Terazono et al. (1988) have isolated a novel gene, reg, i.e. regenerating gene, which is activated in the regenerating islets, as well as a human homolog to reg.