Insulin Resistance in the HIV-Infected Population: The Potential Role of Mitochondrial Dysfunction

Author(s): C. M. Shikuma, L. J. Day, M. Gerschenson.

Journal Name: Current Drug Targets - Infectious Disorders

Volume 5 , Issue 3 , 2005

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Abstract:

Insulin resistance is accepted as the underlying fundamental defect that predates and ultimately leads to the development of type 2 (adult onset) diabetes mellitus in the general non-human immunodeficiency virus (HIV)-infected population. Insulin resistance is also a major component of the metabolic syndrome that, in association with other factors such as hypertension, hypercholesterolemia, and central obesity, defines a pre-diabetic atherogenic state that leads to adverse cardiovascular events. Growing evidence now suggests that mitochondrial dysfunction in skeletal muscle may be the mechanism whereby insulin resistance is induced. The prevalence of insulin resistance, glucose intolerance, and diabetes in the HIV-infected population has dramatically increased following the common use of highly active antiretroviral therapy (HAART). The development of insulin resistance in the HIV-infected population is likely to be multifactorial reflecting genetic predisposition, direct and indirect effects of both the protease inhibitor (PI) and nucleoside reverse transcriptase inhibitor (NRTI) class of antiretroviral therapy, and a possible contribution from chronic inflammatory changes induced by HIV. Indirect effects of antiretroviral therapy on insulin resistance may be mediated through both the visceral adiposity and peripheral fat depletion components of lipodystrophy as well as through fatty infiltration in liver and muscle. Based on current knowledge, mitochondrial dysfunction can be hypothesized to play a key role in each of these components.

Keywords: aids, antiretroviral, diabetes, human immunodeficiency virus, lipodystrophy, mitochondria

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Article Details

VOLUME: 5
ISSUE: 3
Year: 2005
Page: [255 - 262]
Pages: 8
DOI: 10.2174/1568005054880163
Price: $58

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