Reduction of ischemic cell death in cultured Islets of Langerhans by the induction of cytoglobin.

Abstract

Despite the source or mechanism of origin of islets of Langerhans or islet β-cells, all suffer significant cell loss from ischemia after isolation, thereby reducing the surviving islet mass available for study or transplantation. Methods to reduce beta cell death after islet isolation and transplantation must be developed if islet transplantation is to become an accepted treatment for diabetes. In order to enhance intracellular oxygen delivery and utilization, islets were transfected with a plasmid encoding cytoglobin, an intracellular oxygen binding protein. Oxygen consumption, insulin secretion, and the degree of central islet necrosis were measured in untreated and transfected islets to test the effects of cytoglobin on islet survival and function in vitro. The presence of cytoglobin reduced islet cell loss by reducing hypoxia related central islet necrosis and increased insulin secretion as compared with untreated islets. Cytoglobin treated islets maintained a normal rate of oxygen consumption, while untreated islets increased the rate of oxygen consumption caused by a shift to anaerobic metabolism and increased reactive oxygen specie synthesis. The induction of cytoglobin in islets may reduce cell loss from chronic hypoxia and may be a useful adjunct to islet transplantation.