TNFRSF11B and Hypoinsulinemia: Kondegowda et al. (2015) revealed that OPG acted as a β-cell mitogen and enhanced β-cell proliferation in young, aged, and diabetic mice via lactogen mediation. In contrast, Toffoli et al. (2011) reported that mice injected with human recombinant OPG at low doses (1.0 μg/mouse) showed islet inflammation and β-cell death, which led to hypoinsulinemia and hyperglycemia. However, human OPG generated antibodies in rats against the human peptide, which may explain these negative effects (Mochizuki et al., 2002).