Efficient β-cell regeneration by a combination of neogenesis and replication following β-cell ablation and reversal of pancreatic duct ligation.
Achieving efficient β-cell regeneration is a major goal of diabetes research. Previously, we found that a combination of β-cell ablation and pancreatic duct ligation led to β-cell regeneration by direct conversion from α-cells. Here, we studied the effect of surgical reversal of the duct ligation, finding that there was a wave of β-cell replication following reversal. The combination of β-cell neogenesis prior to reversal of the duct ligation and β-cell replication following reversal resulted in efficient β-cell regeneration and eventual recovery of function. This provides an important proof of principle that efficient β-cell regeneration is possible, even from a starting point of profound β-cell ablation. This has important implications for efforts to promote β-cell regeneration.
Sanford Children's Health Research Center, Sanford-Burnham Medical Research Institute, La Jolla, California, USA; Pediatric Diabetes Research Center, University of California, San Diego, California, USA.
Ergeng
E
Hao
Seung-Hee
SH
Lee
Fred
F
Levine
D055011:Ablation Techniques / Q000379:methods*; D000818:Animals; D003920:Diabetes Mellitus / Q000601:surgery*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000601:surgery*; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000378:metabolism; D007515:Islets of Langerhans / Q000601:surgery*; D008026:Ligation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010183:Pancreatic Ducts / Q000601:surgery*
Beta-cells; Diabetes mellitus; Islet of Langerhans; Neogenesis; Regeneration; Replication