- Some HIV drugs that we all take for granted can cause insulin resistance which often leads to diabetes and cardiovascular disease – but why?
Research out of the Washington University School of Medicine in St. Louis shows that protease inhibitors directly interfere with the way blood sugar levels are controlled in the body. This can lead to insulin resistance, this is when your body produces enough insulin but it can’t use it properly.
This problem has had doctors stumped for a while, but these findings provide the potential to develop safer antiviral drugs.
Paul Hruz, MD, PhD, assistant professor of pediatrics and of cell biology and physiology at the School of Medicine, and his team found that first-generation protease inhibitors, including the drug ritonavir, block GLUT4, a protein that transports glucose from the blood into the cells where it is needed. This raises blood sugar levels – a hallmark of diabetes.
“Our lab has established that one of the effects of these drugs is blocking glucose transport, one of most important steps in how insulin works,” says Hruz, senior author of the study published in the Nov. 19 Journal of Biological Chemistry. “Now that we’ve identified the main mechanism, we will look to develop new drugs that treat HIV but don’t cause diabetes.”
Hruz’s lab made the discovery in mice that lacked the GLUT4 protein. When researchers gave these mice ritonavir, the drug had no effect on their glucose tolerance. However, when they gave the drug to normal mice, their blood glucose shot up very quickly, showing that the drugs impair glucose tolerance and promote insulin resistance.
“What we saw were very acute effects on insulin sensitivity that we could reverse in the mice,” Hruz says. “But when insulin resistance goes on for a long time, secondary changes develop, such as high triglycerides, and those are harder to reverse.”
The team is now working with a drug developer on a new HIV drug that does not develop resistance to and does not block GLUT4.