Recombinant betatrophin (Angptl-8/lipasin) ameliorates streptozotocin-induced hyperglycemia and β-cell destruction in neonatal rats

Betatrophin [also known as lipasin, angiopoietin-like 8 (ANGPTL8), refeeding induced in fat and liver (RIFL), or hepatocellular carcinoma-associated gene TD26], a 22-kDa protein in the angiopoietin-like family, is a liver-derived hormone that promotes pancreatic β-cell proliferation and lipid metabolism. The aim of the present study was to investigate the effect of recombinant betatrophin on β-cell regeneration in a neonatal streptozotocin (STZ)-induced diabetic rat model. One-day-old Wistar rats were injected with STZ (100 mg/kg), followed by intraperitoneal administration of betatrophin to the STZ-injected rats for 6 days. Plasma glucose and body weight were monitored. On days 4 and 7, expression levels of pancreatic duodenal homeobox gene-1 (PDX-1), the Bax/B-cell lymphoma-2 (Bcl-2) ratio and plasma insulin were assessed, and the β-cell proliferation rate was determined. Pancreatic islet area and number were determined at 10 weeks. It was found that betatrophin treatment alleviated STZ-induced hyperglycemia, elevated pancreatic expression levels of Bcl-2, PDX-1, plasma insulin levels and the β-cell proliferation rate on days 4 and 7. Long-term betatrophin treatment improved glucose tolerance, associated with improved plasma insulin levels and β-cell mass. These results suggest that early administration of betatrophin promotes β-cell proliferation in STZ-induced diabetic neonates and prevents the development of diabetes in adults.