According to studies conducted by researchers at the Stanford University School of Medicine, a drug that is used to treat metastatic cancer, aflibercept, could be useful in treating diabetes. Studies in rats have shown a link between hypoxia (lack of oxygen) and the ability of liver cells to respond to insulin and it seems that this molecular pathway can be modulated by aflibercept.
Aflibercept is a VEGF, vascular endothelial growth factor, inhibitor, which means is a drug that blocks the proliferation of blood vessels and deprives them of oxygen. So far studies have shown that aflibercept is effective in treating wet macular degeneration and metastatic colorectal cancer; undergoing clinical trials will tell if it can be used to treat metastatic prostate cancer and pulmonary cancer. Dr. Calvin Kuo , MD , PhD, professor of medicine, and his team found that there is a series of protein interactions linking glucose with VEGF inhibitors. He said he was surprised to see that a drug currently used to treat cancer is effective in the management of diabetes in mice and possibly in humans.
The link between VEGF inhibitors and blood glucose level was found several years ago by Dr. Kuo and his team of researchers when they discovered that aflibercept lowered blood sugar levels. Although there are indications that these drugs could have the same effect in humans , no studies have been conducted so far to prove this.
After each meal, glucose passes from blood into cells with the aid of insulin and is stored in the liver as glycogen. When we are hungry again, glycogen is degraded into glucose to meet the needs of the body. There are situations when blood glucose levels rise too high ( hyperglycemia ), and hyperglycemia can occur either when the pancreas does not produce enough insuline (diabetes type 1 ) or when, although there is enough insulin, the body becomes resistant to it ( diabetes type 2 ). For the liver to convert glucose into glycogen, cells must have enough oxygen. Hypoxic cells (ie those that are deprived of oxygen ) produce certain proteins that help them survive in such conditions.
Now researchers have found that one of these proteins, HIF- 2alpha, stimulates the expression of IRS2, insulin receptor substrate 2, which increases the ability of cells to respond to insulin. “Much work remains to translate these mouse studies to human patients, but it will be interesting to explore VEGF inhibitors or drugs that can stabilize HIF-2alpha, such as prolyl hydroxylase inhibitors, for diabetes treatment“, explained Kuo.