Enhancement of β-Cell Regeneration by Islet Transplantation After Partial Pancreatectomy in Mice

Abstract

Pancreatic beta cells are known to regenerate, especially when insulin requirements are increased. Islet transplantation (ITx) is one strategy for insulin replacement in patients with diabetes. ITx can provide not only insulin in a physiological manner but also can exert additional effects such as beta-cell regeneration. This study examined the effects of ITx on endogenous beta-cell mass in mice. Male Balb/c mice were 70% pancreatectomized and transplanted with syngeneic islets, then compared with pancreatectomized mice with or without insulin treatment. Blood glucose levels and weight were evaluated for 10 days, with remnant pancreas obtained for evaluation of beta-cell mass and turnover. Hyperglycemia and weight loss were induced after pancreatectomy (Px). After ITx or insulin treatment, blood glucose levels recovered to normal, and body weight started to increase. At 10 days after Px, fasting serum insulin levels, beta-cell mass, and insulin content in the remnant pancreas were higher in the ITx group than they were in the Px group. Insulin treatment after Px also increased beta-cell mass, but did not increase pancreatic insulin content compared with those in the Px group. The enhanced beta-cell mass and insulin content in the remnant pancreas of the ITx group resulted from increased beta-cell proliferation/neogenesis and from prevention of beta-cell apoptosis. These findings suggest that ITx after partial Px in mice enhances endogenous beta-cell regeneration and survival, rendering beta-cell mass increased and glucose homeostasis improved.