Absence of spontaneous regeneration of endogenous pancreatic β-cells after chemical-induced diabetes and no effect of GABA on α-to-β cell transdifferentiation in rhesus monkeys

Abstract

β-cell deficiency is common feature of type 1 and late-stage of type 2 diabetes mellitus. Thus, β−cell replacement therapy has been the focus of regenerative medicine past several decades. Particularly, evidences suggest that β−cell regeneration via transdifferentiation from sources including α-cells is promising. However, data using higher mammals besides rodents are scarce. Here, we examined whether endogenous pancreatic β-cells could regenerate spontaneously or under normoglycemia following porcine islet transplantation for varied periods up to 1197 days after streptozotocin-induced diabetes, and remaining α-cells transdifferentiate into β-cells by GABA treatment in vivo and in vitro. The results showed that endogenous β-cells rarely regenerate in both conditions as evidenced by stagnant serum C-peptide levels and β-cell number in the pancreas, and the remaining α-cells did not transdifferentiate into β-cells by GABA treatment. Collectively, we concluded that monkey β-cells had relatively low regenerative potential compared with rodent counterpart and GABA treatment could not induce α-to-β-cell transdifferentitation.