Navigation Links
HIV drugs interfere with blood sugar, lead to insulin resistance
Date:11/22/2010

The same powerful drugs that have extended the lives of countless people with HIV come with a price insulin resistance that can lead to diabetes and cardiovascular disease.

Now, researchers at Washington University School of Medicine in St. Louis have determined why that happens. Their research shows that HIV protease inhibitors directly interfere with the way blood sugar levels are controlled in the body. This leads to insulin resistance, a condition that occurs when the body produces enough insulin but doesn't use it properly.

This confirmation provides 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," he says.

The finding will help researchers better understand the role of glucose transporters in health and disease, including the epidemic of type 2 diabetes in HIV negative patients, says Hruz. He expects the results will help scientists better understand how to develop new diabetes drugs and the role of glucose transport in diseases such as heart failure.

Hruz and his team are now studying at the molecular level how the HIV drugs inhibit GLUT4.

"We'd like to figure out exactly how these drugs interact with the transporter to aid the development of better HIV drugs," he says. "We want to find problems in glucose transport that lead to diabetes in the preclinical stage of drug development."

The team already is working with a drug developer to create a new HIV drug that the virus does not develop resistance to and does not block GLUT4.


'/>"/>

Contact: Beth Miller
millerbe@wustl.edu
314-286-0119
Washington University School of Medicine
Source:Eurekalert

Related biology news :

1. Cholesterol-lowering drugs and the effect on muscle repair and regeneration
2. Vitamin C supplements may reduce benefit from wide range of anti-cancer drugs
3. Discovering drugs, biofuels in tropical seas
4. Academy participates in project to discover drugs, biofuels in tropical seas
5. European researchers harness unique properties of boron to develop new drugs and diagnostics
6. Self-assembling nano-fiber gel delivers high concentrations of clinically approved drugs
7. Moderate use averts failure of type 2 diabetes drugs in animal model
8. Montana State University researchers find gene that regulates molds resistance to drugs
9. MSU researcher studies ties between cholesterol drugs, muscle problems
10. New technique eliminates toxic drugs in islet transplant in diabetic mice
11. REGiMMUNE receives $12 million in grants to develop transplant and allergy drugs
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/23/2017)... N.Y. and ITHACA, N.Y. ... ) and Cornell University, a leader in dairy research, ... with bioinformatics designed to help reduce the chances that ... With the onset of this dairy project, Cornell University ... Consortium for Sequencing the Food Supply Chain, a food ...
(Date:5/16/2017)... , May 16, 2017  Veratad Technologies, LLC ... of online age and identity verification solutions, announced today ... Identity Conference 2017, May 15 thru May 17, 2017, ... Building and International Trade Center. Identity ... globe and in today,s quickly evolving digital world, defining ...
(Date:4/24/2017)... 2017 Janice Kephart , former ... Strategy Partners, LLP (IdSP) , today issues the ... Trump,s March 6, 2017 Executive Order: Protecting ... can be instilled with greater confidence, enabling the ... refugee applications are suspended by until at least ...
Breaking Biology News(10 mins):
(Date:7/18/2017)... ... , ... Sourcing custom glass or quartz parts can be a daunting task. ... execute your job can take many hours of emails, phone calls and on-line research. ... showcase the company’s capabilities and core custom categories, and enables you to start the ...
(Date:7/18/2017)... ... July 18, 2017 , ... G-CON today announced that ... Office for its Patent Applications 14/858,857 and 13/669,785 both entitled Modular, Self-Contained, Mobile ... further expand the protection of G-CON’s R&D investments and validate the G-CON platform ...
(Date:7/18/2017)... ... July 18, 2017 , ... Allotrope Foundation ... the first phase of the Allotrope Framework for commercial use. , The Bio-IT ... to “not only elevate the critical role of information technology in modern biomedical ...
(Date:7/17/2017)... ... ... Whitehouse Laboratories is excited to announce that it has ... ISO 80369 standard test procedures. The ISO 80369 series of eight test standards ... this recent expansion, Whitehouse Labs becomes one of the only facilities in the ...
Breaking Biology Technology: