Can splenocytes enhance pancreatic beta-cell function and mass in 90% pancreatectomized rats fed a high fat diet?

Aims: Recent studies have shown that splenocytes may act as a possible neogenic source with regard to beta-cells in rodent diabetic models. Accordingly, we sought to determine whether splenocytes played an important role in promoting beta-cell function and mass among type 2 diabetic rats with and without spleen.

Main Methods: We randomly divided female 90% pancreatectomized (Px) Sprague Dawley rats into three groups: splenectomy (SPX), splenectomy plus the injection of male splenocytes (SPI), and no splenectomy (NSP). They were administered with 40 energy percent fat diets over the course of five weeks. At the end of the experimental period, insulin secretion capacity was measured by hyperglycemic clamp. At 6 h after BrdU(+) injection, the pancreas was prepared with 4% paraformaldehyde in order to perform immunohistochemistry.

Key Findings: SPX increased and sustained serum glucose levels more than NSP and SPI during oral glucose tolerance testing. During hyperglycemic clamp, first and second phase insulin secretion decreased in the SPX rats while splenocyte injections counteracted this. Beta-cell mass in the SPX group was reduced more than among NSP and SPI. This was the result of a decrease in the number of small beta-cell clusters in SPX, which is indicative of a decrease in beta-cell neogenesis.

Significance: Splenocytes play an important role with regard to the neogenesis of beta-cells in insulin deficient type 2 diabetic rats, although they are not critical for beta-cell regeneration.