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

Abstract

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.

Analysis of the Expression and Prognostic Potential of a Novel Metabolic Regulator ANGPTL8/Betatrophin in Human Cancers

“…ANGPTL8/betatrophin seemes to be a pleiotropic hormone, as it was reported to regulate both lipid and glucose metabolism [2][3][4][5][6], and was recently reported to act as a moderate suppressor of human liver carcinoma cells [19]. ANGPTL8/betatrophin is not only enriched in the liver but is also reported to be expressed at significantly higher levels in hepatocellular carcinoma patients than in healthy controls [18].…”

“…In the present study, it was referred to as ANGPTL8/betatrophin. Previous studies have shown that ANGPTL8/betatrophin is involved in the regulation of both lipid metabolism and glucose homeostasis [3][4][5][6]. It is well known that cancer cells change their metabolism to support rapid proliferation and expansion; hence, abnormal lipid and glucose metabolism has been found to be involved in a variety of cancers [7][8][9][10][11].…”

Hyperbaric oxygen treatment improves pancreatic β‑cell function and hepatic gluconeogenesis in STZ‑induced type‑2 diabetes mellitus model mice

“…Subsequently, the mice were sacrificed by exsanguination following an intraperitoneal injection of 50 mg/kg sodium pentobarbital. Blood samples were obtained from the orbital sinus and stored at −20°C or −80°C until further use ( 18 , 19 ).…”