STANFORD, Calif. A pair of studies by researchers at the Stanford University School of Medicine has identified a molecular pathway a series of interaction among proteins involved in the development of diabetes. Furthermore, they have found that a drug already approved for use in humans can regulate the pathway.
The findings will be published online Sept. 15 in two articles in Nature Medicine.
The studies, done in mice, identify a previously unexpected link between a low-oxygen condition called hypoxia and the ability of cells in the liver to respond to insulin. The drug, aflibercept (marketed as Eylea or Zaltrap), is used to treat metastatic colorectal cancer and a form of macular degeneration. Aflibercept is a member of a family of proteins that inhibit the vascular endothelial growth factor, or VEGF, pathway. It works by blocking the growth of the blood vessels into tumors and starving them of oxygen.
The lab of Calvin Kuo, MD, PhD, professor of medicine, identified a series of protein interactions that link VEGF inhibitors and blood glucose levels. "We were surprised to find that this drug currently used in patients for cancer treatment had beneficial effects on diabetes in laboratory mice and could, potentially, in humans," said Kuo, senior author of one of the Nature Medicine papers.
Amato Giaccia, PhD, the Jack, Lulu and Sam Willson Professor of Cancer Biology, is senior author of the other paper. "Proteins involved in this pathway could also be targeted for the development of new diabetes therapies," said Giaccia, who also is a professor and director of radiation oncology. His laboratory has identified a protein called PhD3 that could be a particularly attractive target.
The lead author of the Giaccia paper is Cullen Taniguchi MD, PhD, a radiation oncology resident at Stanford; former graduate students Kevin Wei, MD, PhD, and Lisa McGinnis, MD, PhD, and postdoctoral scholar Stephanie Piecewicz, PhD, a
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Stanford University Medical Center