Our data show that insulin exposure significantly reduces the average BIBW2992 expression of genes in the electron transport chain, with significant enrichment in GO group I: NADH dehydrogenase activity. These findings emphasize that electron transport chain is significantly regulated by insulin and, probably, negatively regulated by the chronic exposure to elevated concentrations of the hormone. Indeed, it has been shown that insulin not only regulates this pathway but also that, in the presence of insulin resistance, electron transport chain can be deeply altered. In conclusion, the present data demonstrate that insulin affects mRNA levels of about 1700 genes in HUVECs. These genes can be clustered in groups with characteristic time expression profile and classified into functional categories that can support the biological effects of insulin. Microarray data were confirmed by measuring the mRNA levels of a subset of genes using quantitative real-time PCR. An important issue now is to understand how insulin coordinates the expression of all these genes. The identification of common elements in the promoter sequences of group of genes will help the discovery of the transcription factors linking the effect of insulin on multiple genes simultaneously. In addition, since chronic hyperinsulinemia contributes to the instability of the atherosclerotic plaque and stimulates cellular proliferation, some of the genes identified in the present work are potential novel candidates in diabetes complications related to endothelial dysfunction. More focused studies on subsets of genes and on several donors will be objective of future studies. Traditionally, many different cell types within a tumor have been considered to have tumorigenic potential and possess the ability to cause cancers in secondary recipients. By contrast, the cancer stem cell hypothesis suggests that only a small subpopulation of tumor cells has that potential. This hypothesis has been shown consistent with data from such diverse cancer types as chronic and acute myeloid leukemias, breast cancer, colorectal cancer, mesenchymal neoplasms, head and neck squamous cell carcinoma, and pancreatic cancer. The investigation of cancer stem cells in melanoma, however, has led to controversial findings. Some studies suggested that melanoma cells that are capable of transplanting the disease are exceedingly rare while others, using more severely immunocompromised mice, found that cells with those capabilities are very common within the tumor. Similarly, the frequency of tumor cells positive for stem cell-like markers in breast cancer varies according to the stage and subtype of the tumor. These findings have led to discussions about the applicability of the cancer stem cell hypothesis to all tumor types, and also the ability of xenotransplantation.