AIDSWEEKLY Plus; Monday, May 25, 2009
Staff Medical Writers

2009 MAY 25 - (NewsRx.com) -- "Zhang S, Carper MJ, Lei X, Cade WT, Yarasheski KE, Ramanadham S. Protease inhibitors used in the treatment of HIV+ induce beta-cell apoptosis via the mitochondrial pathway and compromise insulin secretion. Am J Physiol Endocrinol Metab 296: E925-E935, 2009," scientists in the United States report (see also HIV/AIDS).

"First published February 10, 2009; doi:10.1152/ajpendo.90445.2008. Inclusion of HIV protease inhibitors (PIs) in the treatment of people living with HIV+ has markedly decreased mortality but also increased the incidence of metabolic abnormalities, causes of which are not well understood. Here, we report that insulinopenia is exacerbated when Zucker fa/fa rats are exposed to a PI for 7 wk, suggesting that chronic PI exposure adversely affects pancreatic islet beta-cell function. In support of this possibility, we find increased apoptosis, as reflected by TUNEL fluorescence analyses, and reduced insulin-secretory capacity in insulinoma cells and human pancreatic islet cells after in vitro exposures (48-96 h) to clinically relevant PIs (ritonavir, lopinavir, atazanavir, or tipranavir). Furthermore, pancreatic islets isolated from rats administered an HIV-PI for 3 wk exhibit greater cell death than islets isolated from vehicle-administered rats. The higher incidence of HIV-PI-induced cell death was associated with cleavage and, hence, activation of caspase-3 and poly(ADP)-ribose polymerase but not with activation of phospho-pancreatic endoplasmic reticulum (ER) kinase or induction of ER stress apoptotic factor C/EBP homologous protein. Exposure to the HIV-PIs, however, led to activation of mitochondria-associated caspase-9, caused a loss in mitochondrial membrane potential, and promoted the release of cytochrome c, suggesting that HIV-PIs currently in clinically use can induce beta-cell apoptosis by activating the mitochondrial apoptotic pathway," wrote S. Zhang and colleagues, Washington University, Medical Department.

The researchers concluded: "These findings therefore highlight the importance of considering beta-cell viability and function when assessing loss of glycemic control and the course of development of diabetes in HIV+ subjects receiving a protease inhibitor."

Zhang and colleagues published their study in American Journal of Physiology - Endocrinology and Metabolism (Protease inhibitors used in the treatment of HIV+ induce beta-cell apoptosis via the mitochondrial pathway and compromise insulin secretion. Am J Physiol Endocrinol Metab. 2009 Apr;296(4):E925-35).

For additional information, contact S. Ramanadham, Washington University, School Medical, Dept. of Internal Medical, Division Endocrinol Metab & Lipid Research, 660 S Euclid Avenue, Box 8127, St. Louis, MO 63110, USA.

The publisher's contact information for the American Journal of Physiology - Endocrinology and Metabolism is: American Physiological Society, 9650 Rockville Pike, Bethesda, MD 20814, USA.

Keywords: United States, Box, HIV/AIDS, AIDS, Acquired Immune Deficiency Syndrome, Acquired Immunodeficiency Syndrome, Apoptosis, Drugs, Endocrinology, Enzymology, Gastroenterology, HIV, Human Immunodeficiency Virus, Immunology, Insulinoma, Metabolism, Pancreas, Pharmaceuticals, Physiology, Protease Inhibitor, Protease Inhibitors, Ritonavir, Sexually Transmitted Disease, Therapy, Treatment, Viral, Virology, Washington University, Medical Department.

This article was prepared by AIDS Weekly editors from staff and other reports. Copyright 2009, AIDS Weekly via NewsRx.com.

2009-05-25
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