Biochemical and Biophysical Research Communications, Vol.508, No.4, 1056-1061, 2019
Absence of spontaneous regeneration of endogenous pancreatic beta-cells after chemical-induced diabetes and no effect of GABA on alpha-to-beta cell transdifferentiation in rhesus monkeys
beta-cell deficiency is common feature of type 1 and late-stage of type 2 diabetes mellitus. Thus, beta-cell replacement therapy has been the focus of regenerative medicine past several decades. Particularly, evidences suggest that beta-cell regeneration via transdifferentiation from sources including alpha-cells is promising. However, data using higher mammals besides rodents are scarce. Here, we examined whether endogenous pancreatic beta-cells could regenerate spontaneously or under normoglycemia following porcine islet transplantation for varied periods up to 1197 days after streptozotocin-induced diabetes, and remaining alpha-cells transdifferentiate into beta-cells by GABA treatment in vivo and in vitro. The results showed that endogenous beta-cells rarely regenerate in both conditions as evidenced by stagnant serum C-peptide levels and beta-cell number in the pancreas, and the remaining alpha-cells did not transdifferentiate into beta-cells by GABA treatment. Collectively, we concluded that monkey beta-cells had relatively low regenerative potential compared with rodent counterpart and GABA treatment could not induce alpha-to-beta-cell transdifferentitation. (C) 2018 Elsevier Inc. All rights reserved.