Effects Of Betatrophin On The Proliferation Of β Cells In Newborn Rats With Type 1 Diabetes Mellitus

Purpose: Betatrophin, a newly identified hormone, has been introduced to promote β cell proliferation and improve glucose tolerance in insulin resistance mouse model. The purpose of the study is to explore the effects of betatrophin on β cells in streptozotocin- induced type 1 diabetic rats(T1DM).Methods: Streptozotocin(STZ, 100mg/kg body weight, bw) was given to newborn rats to establish the T1 DM model, followed by 5 days of consecutive treatment with betatrophin(300?g/kg.bw). Plasma glucose, insulin levels, and body weight were monitored. The survival rate of STZ-treated neonates, with or without betatrophin, was calculated on day 7. Protein levels of the anti-apoptosis factor Bcl-2 and insulin promoter factor PDX-1 in the pancreas were determined with Western Blotting. β cell proliferation rates, calculated by β cell co- localization with K i67 and insulin detected via double- immunofluorescence staining, were also used to determine the role of betatrophin in STZ- induced diabetes.Results: Plasma glucose peaked(22.59±2.22mmol/l) on day 4 and declined substantially by day 7(12.25±1.8mmol/l) in STZ- induced diabetic rats, whereas betatrophin treatment alleviated STZ- induced hyperglycemia on day 4(16.49±1.49mmol/l) and day 7(8.79±0.76mmol/l). The survival rate of diabetic neonates improved from 64% to 100% with betatrophin treatment. Pancreatic levels of Bcl-2 and PDX-1 increased on day 7 in betatrophin- treated diabetic rats, and the number of K i67 and insulin double-immunoreactive cells in those rats increased compared with rats administered STZ alone.Conclusion: Betatrophin ameliorates hyperglycemia, enhances survival rates, and promotes β cell proliferation in STZ- induced type 1 diabetic rats.