Recombinant Reg3α Prevents Islet β-Cell Apoptosis and Promotes β-Cell Regeneration

Authors:
Open Access
Publisher website
Google Scholar
Abstract
Progressive loss and dysfunction of islet β-cells has not yet been solved in the treatment of diabetes. Regenerating protein (Reg) has been identified as a trophic factor which is demonstrated to be associated with pancreatic tissue regeneration. We previously produced recombinant Reg3α protein (rReg3α) and proved that it protects against acute pancreatitis in mice. Whether rReg3α protects islet β-cells in diabetes has been elusive. In the present study, rReg3α stimulated MIN6 cell proliferation and resisted STZ-caused cell death. The protective effect of rReg3α was also found in mouse primary islets. In BALB/c mice, rReg3α administration largely alleviated STZ-induced diabetes by the preservation of β-cell mass. The protective mechanism could be attributed to Akt/Bcl-2/-xL activation and GRP78 upregulation. Scattered insulin-expressing cells and clusters with small size, low insulin density, and exocrine distribution were observed and considered to be neogenic. In isolated acinar cells with wheat germ agglutinin (WGA) labeling, rReg3α treatment generated insulin-producing cells through Stat3/Ngn3 signaling, but these cells were not fully functional in response to glucose stimulation. Our results demonstrated that rReg3α resists STZ-induced β-cell death and promotes β-cell regeneration. rReg3α could serve as a potential drug for β-cell maintenance in anti-diabetic treatment.
Funding Information
  • National Natural Science Foundation of China (81603014, 32100910)
  • China Postdoctoral Science Foundation (2019M652036)
  • Priority Academic Program Development of Jiangsu Higher Education Institutions
  • National Science and Engineering Council of Canada (RGPIN-2017-05246)
  • Canadian Institutes of Health Research (PJT-175208)
  • “National Mentorship” training program for Suzhou Youth Health Key Talent (Qnng2021030)
  • National Science Foundation for Young Scientists of China (81602919)
  • 5th Suzhou Health Talent Program (GSWS2019071)
  • Medical Scientific Research Key Project of Jiangsu Commission of Health (M2021054)

This publication has 49 references indexed in Scilit: