Insulin Resistance among HIV-Infected Patients: Unraveling the Mechanism

ArticleinClinical Infectious Diseases 41(9):1341-2 · December 2005with2 Reads
DOI: 10.1086/496990 · Source: PubMed
    • "Our results support the hypothesis that lactate is not a mere byproduct of glycolysis without relevant metabolic roles. In fact, several groups have shown that lactate metabolism is highly versatile and associated with several pathological conditions262728293031. The inhibitory effects of lactate on the enzymes known to be important in regulating glycolytic flux, such as hexokinase and PFK, in tissues, such as skeletal muscle and liver, can have a inhibitory effect on carbohydrate metabolism [14, 15, 17]. "
    [Show abstract] [Hide abstract] ABSTRACT: We examined the effects of lactate on the enzymatic activity of hexokinase (HK), phosphofructokinase (PFK) and pyruvate kinase (PK) in various mouse tissues. Our results showed that lactate inhibited PFK activity in all the analyzed tissues. This inhibitory effect was observed in skeletal muscle even in the presence of insulin. Lactate directly inhibited the phosphorylation of PFK tyrosine residues in skeletal muscle, an important mechanism of the enzyme activation. Moreover, lactate indirectly inhibited HK activity, which resulted from its cellular redistribution, here attributed to alterations of HK structure. PK activity was not affected by lactate. The activity of HK and PFK is directly related to glucose metabolism. Thus, it is conceivable that lactate exposure can induce inhibition of glucose consumption in tissues.
    Full-text · Article · Nov 2010
  • [Show abstract] [Hide abstract] ABSTRACT: With the advent of highly active antiretroviral therapy (HAART) in mid-1995, the prognosis for HIV-infected individuals has brightened dramatically. However, the conjunction of potent antiviral therapy and longer life expectancy may engender a variety of health risks that, heretofore, HIV specialists have not had to confront. The long-term effects of HIV infection itself and exposure to antiretroviral agents is unknown. Several aspects of aging, including psychiatric disease, neurocognitive impairment, and metabolic and hormonal disorders, may be influenced by chronic exposure to HIV and/or HIV therapeutics. In this paper, we discuss the health issues confronting HIV-infected older adults and areas for future research.
    Full-text · Article · Feb 2006
  • [Show abstract] [Hide abstract] ABSTRACT: Cardiovascular risk factors, including the fat redistribution syndrome, dyslipidaemia, insulin resistance and diabetes mellitus, have been increasingly described in association with new potent protease inhibitor-based antiretroviral therapies in patients with HIV infection. The introduction of highly active antiretroviral therapy (HAART) in clinical practice has altered the natural history of HIV remarkably, leading to a notable extension of life expectancy, and prolonged lipid and glucose metabolism abnormalities are expected to lead to significant effects on the long-term prognosis and outcome of HIV-infected patients. Prediction modelling, surrogate markers and hard cardiovascular end points suggest an increased incidence of cardiovascular diseases in HIV-infected subjects receiving HAART, even though the absolute risk of cardiovascular complications remains low, and must be balanced against the evident virological, immunological and clinical benefits descending from combination antiretroviral therapy. Nevertheless, the assessment of cardiovascular risk should be performed on a regular basis in HIV-positive individuals, especially after initiation or change of antiretroviral treatment. Appropriate lifestyle measures (including smoking cessation, dietary changes and aerobic physical activity) are critical points, and switching HAART may be considered, although maintaining viremic control should be the main goal of therapy. Pharmacological treatment of dyslipidaemia (usually with statins and fibrates) and hyperglycaemia (with insulin-sensitising agents and thiazolidinediones) becomes suitable when lifestyle modifications and switching therapy are ineffective or not applicable.
    Article · Oct 2006
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