UCSF

Beta cell dysfunction is a major contributor to the pathogenesis of type 2 diabetes. This dysfunction, which results in the inability of the beta cell to produce and secrete insulin upon elevations in blood glucose, has been linked to various metabolic and mitochondrial insults. It has been previously been shown that perturbations of the iron metabolism and mitochondrial iron-sulfur (Fe-S) cluster biogenesis and transport may lead to beta cell dysfunction; we therefore sought to explore the role of the mitochondrial Fe-S cluster protein BOLA3 in beta cell metabolism and function. In this study we determine that beta cell-specific loss of Bola3 in both murine and human beta cells results in a gradual perturbation of glucose homeostasis and beta cell degradation. Our data further indicate that both treatment with exogenous recombinant BOLA3 protein and supraphysiological expression of endogenous Bola3 improves glucose-stimulated insulin secretion in beta cells, thereby establishing a potential therapeutic role for Bola3 and other regulators of mitochondrial metabolism in type 2 diabetes.