Dynamic Changes of Betatrophin and Its Potential Effect on β-cells in Spontaneously Developed or Streptozocin-induced Diabetes Monkeys

Effects of betatrophin on β-cell proliferation and insulin secretion have been reported controversially in rodent studies. This study was to investigate the dynamic changes of betatrophin and its potential effect on β-cell function in non-human primates (NHPs). Blood betatrophin levels in naturally developed diabetes cynomolgus monkeys (n=65) significantly correlated with their body weights and blood glucose levels in the females (n=20) and with insulin and C-peptide levels in the males (n=45). Liver expression of betatrophin mRNA was markedly higher in spontaneously developed diabetes monkeys than in normoglycemic ones. Its liver expression correlated well with islet size and insulin content in normoglycemic cynomolgus monkeys and also well in spontaneously hyperglycemic (>200 mg/ dL) cynomolgus monkeys with high blood insulin level, but not well in those with very low blood insulin content. Both blood glucose and betatrophin increased dramatically in normoglycemic rhesus monkeys (n=7) after streptozocin (STZ) administration. Blood insulin initially increased on day 1 after STZ dosing and then decreased dramatically. Two NHPs with blood glucose back to ~80 mg/mL on day 14 after STZ injection showed recovery of insulin secretion. In another two STZ-treated NHPs with blood glucose >250 mg/dL, apparent proliferation of both β-cells and non-βcells was observed in their islets. The rest NHPs with more completed β-cell destruction after STZ dosing showed much higher blood glucose (>300 mg/dL) with very low insulin and no obvious β-cell proliferation. Our results indicate that NHP liver expresses abundant betatrophin mRNA. As its levels correlated well with islet size and insulin content in some diabetic NHPs, it might play a role in β-cell proliferation. Our data are consistent with the clinical finding of the elevation of circulating betatrophin in patients with type 2 diabetes. In addition, betatrophin-enhanced β-cell proliferation seems requiring a minimal base level of pancreatic β-cells and islets. Dynamic Changes of Betatrophin and Its Potential Effect on β-cells in Spontaneously Developed or Streptozocin-induced Diabetes Monkeys Yongqiang Liu1, Xiaoli Wang1, Bingdi Wang1, Guofeng Sun1, Francine Gregoire2, Keefe Chng2, Jinhu Wang3, Yixin (Jim) Wang1,2 and Yong-Fu Xiao1* 1Cardiovascular and Metabolic Diseases Research, Crown Bioscience Inc., 6 Beijing West Road, Science & Technology Park, Taicang Economic Development Area, Taicang, Jiangsu Province 215400, P.R. China 2International Institute of Biomedical Research (IIBR), a Crown Bioscience Company at David H. Murdock Research Institute (DHMRI), Kannapolis, NC, USA 3Department of Laboratory Medicine, Taicang Affiliated Hospital of Soochow University, Taicang, China *Corresponding author: Yong-Fu Xiao, MD, PhD, Cardiovascular and Metabolic Diseases Research, Crown Bioscience Inc., 6 Beijing West Road, Science & Technology Park, Taicang Economic Development Area, Taicang, Jiangsu Province 215400, P.R. China, Tel: +86-512-5387-9826; Email: [email protected] Received December 05, 2016; Accepted December 26, 2016; Published December 30, 2016 Citation: Yongqiang Liu, Xiaoli Wang, Bingdi Wang, Guofeng Sun, Francine Gregoire, et al. (2016) Dynamic Changes of Betatrophin and Its Potential Effect on β-cells in Spontaneously Developed or Streptozocin-induced Diabetes Monkeys. J Diabetes Metab 7: 719. doi: 10.4172/2155-6156.1000719 Copyright: © 2016 Yongqiang Liu, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.