Gastrin treatment stimulates {beta}-cell regeneration and improves glucose tolerance in 95% pancreatectomized rats.

摘要

beta-Cell mass reduction is a central aspect in the development of type 1 and type 2 diabetes, and substitution or regeneration of the lost beta-cells is a potentially curative treatment of diabetes. To study the effects of gastrin on beta-cell mass in rats with 95% pancreatectomy (95%-Px), a model of pancreatic regeneration, rats underwent 95% Px or sham Px and were treated with [15 leu] gastrin-17 (Px+G and S+G) or vehicle (Px+V and S+V) for 15 d. In 95% Px rats, gastrin treatment reduced hyperglycemia (280 +/- 52 mg vs. 436 +/- 51 mg/dl, P < 0.05), and increased beta-cell mass (1.15 +/- 0.15 mg)) compared with vehicle-treated rats (0.67 +/- 0.15 mg, P < 0.05). Gastrin treatment induced beta-cell regeneration by enhancing beta-cell neogenesis (increased number of extraislet beta-cells in Px+G: 0.42 +/- 0.05 cells/mm(2) vs. Px+V: 0.27 +/- 0.07 cells/mm(2), P < 0.05, and pancreatic and duodenal homeobox 1 expression in ductal cells of Px+G: 1.21 +/- 0.38% vs. Px+V: 0.23 +/- 0.10%, P < 0.05) and replication (Px+G: 1.65 +/- 0.26% vs. S+V: 0.64 +/- 0.14%; P < 0.05). In addition, reduced beta-cell apoptosis contributed to the increased beta-cell mass in gastrin-treated rats (Px+G: 0.07 +/- 0.02%, Px+V: 0.23 +/- 0.05%; P < 0.05). Gastrin action on beta-cell regeneration and survival increased beta-cell mass and improved glucose tolerance in 95% Px rats, supporting a potential role of gastrin in the treatment of diabetes.