November 24, 2010
Researchers at St. Louis' Washington University (WU) may have shed light on how protease inhibitors could contribute to insulin problems seen in some patients.
In mouse studies, researchers at WU's School of Medicine found that the first-generation protease inhibitor ritonavir appears to inhibit a key mechanism known as glucose transporter 4, a protein that transports glucose to cells that need it. In mice genetically altered to lack the glucose transporter, known as GLUT4, the introduction of ritonavir did not exacerbate the observed glucose intolerance. In control mice, however, ritonavir did impair glucose tolerance.
Similarly, ritonavir reduced peripheral insulin sensitivity in control mice but not in mice lacking GLUT4.
"Now that we've identified the main mechanism, we will look to develop new drugs that treat HIV but don't cause diabetes," said Paul Hruz, a WU professor of pediatrics and biology who led the team.
The full study, "Effects of the HIV Protease Inhibitor Ritonavir on GLUT4 Knock-Out Mice," was published in the Journal of Biological Chemistry (2010;285:36395-36400).
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