The investigators hypothesize that mitochondrial DNA damage from uteroplacental insufficiency via the production of reactive oxygen species (ROS) results in further escalation of genetic damage in the mitochondria, specifically in deletions. A self-reinforcing cycle of progressive deterioration in mitochondrial function leads to a corresponding decline in beta-cell function. Finally, a threshold in mitochondrial dysfunction and ROS production is reached and beta-cell death occurs. The onset of diabetes ensues when a critical level of abnormal beta-cell insulin secretion combined with beta-cell loss is reached. It will be tested whether uteroplacental insufficiency causes mitochondrial dysfunction, oxidative stress, and deletions in mtDNA in the beta-cell, and that these effects act synergistically to lead to the development of beta-cell failure and type II diabetes. To link the damage to the mitochondria caused by uteroplacental insufficiency to the beta-cell phenotype observed in type II diabetes, the investigators will induce beta-cell failure in vitro by transferring damaged mitochondria from IUGR animals into beta-cells from unaffected, non-IUGR animals
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