Cerebral glucose transporter expression in HIV infection

Abstract

Abnormalities in cerebral glucose metabolism have been demonstrated in patients with AIDS dementia complex (ADC), with increased consumption in early disease and decreased utilization in late stages. The basis of these changes is unknown. Accordingly, a pilot study was undertaken to determine whether levels of cerebral glucose transporters GLUT1 and GLUT3 were altered by HIV disease. Frontal gray and white matter membrane preparations from patients with HIV encephalitis (HIVE), HIV infection without parenchymal neuropathology, and non-infected controls were utilized in quantitative immunoblots to measure GLUT1 and GLUT3. Results were expressed as a ratio of glucose transporter to structural protein actin. Within-group patient variability was great, precluding statistically significant differences between groups for any one brain region. However, when data for gray and white matter was pooled, results obtained statistical significance, with levels of GLUT1 increasing in HIV infection without neuropathology, and declining with HIVE. Increased GLUT1 in HIV infection without parenchymal neuropathology may be important in the biology of increased glucose consumption described with early ADC. With progression to HIVE, reduced levels of glucose transporters may contribute to late stage hypometabolism.

Genetic and Metabolic Control of the Mitochondrial Transmembrane Potential and Reactive Oxygen Intermediate Production in HIV Disease

“…Accordingly, increased oxidative stress in HIV-infected donors is accompanied by increased glucose utilization both on the cellular (Sorbara et al, 1996) and organismal levels (Rottenberg et al, 1996;Kovitz and Morgello, 1997;Lutz et al, 1997) (Table 3). Increased glucose utilization is supported by enhanced expression of glucose transporter GLUT1 in HIV-infected H9 cells (Sorbara et al, 1996) and in the HIV-infected brain (Kovitz and Morgello, 1997). Of note, oxidative stress results in elevated GLUT1 expression (Kozlovsky et al, 1997).…”

“…These latter observations point out the significance of soluble mediators of oxidative stress, such as increased TRX and pro-apoptotic cytokines, TNF-a, and IL-1. Alternatively, deficiencies in cysteine/GSSG , purine (Tabucchi et al, 1994;Bofill et al, 1995), and glucose metabolism (Rottenberg et al, 1996;Sorbara et al, 1996;Lutz et al, 1997;Kovitz and Morgello, 1997) may also contribute to generalized oxidative stress and bystander cell death. Resolution of these controversial issues will help understand the pathogenesis of HIV disease.…”

“…Resting energy expenditure (REE) of HIV-infected subjects is elevated with disease pro- Sharpstone et al, 1996;Mulligan and Bloch, 1998) Altered glucose metabolism Brain, gut (Rottenberg et al, 1996;Lutz et al, 1997) Enhanced expression of glucose transporter HIV-infected H9 cells, brain (Sorbara et al, 1996;Kovitz and Morgello, 1997) Increased uptake of vitamin C Monocytic and T cell lines (Rivas et al, 1997) Decreased phosphatidylinositol metabolism HIV-infected peripheral blood T cells (Hofmann et al, 1990) Decreased de novo ribonucleotide synthesis HIV-infected peripheral blood T cells (Bofill et al, 1995) Decreased adenylate/guanylate ratio HIV-infected peripheral blood T cells (Tabucchi et al, 1994) gression (Grunfeld et al, 1992). Multiple factors, including opportunistic infections, malabsorption, diarrhea, medications, and altered metabolism, contribute to a generalized wasting and loss of lean body and muscle mass (Kaminski, Jr. et al, 1998).…”

Oxidative Stress during HIV Infection: Mechanisms and Consequences

“…The inhibitory effects of antioxidant treatment could also be attributed to the ability of ROS to induce CXCR4 receptor [150] as well as the glucose transporter Glut1 [151]. Enhanced expression of Glut1 was observed in both the infected cell cultures [152] and the neuronal tissues of the patients [153]. It leads to the elevation of glucose influx into the lymphocytes, monocytes, and epithelial cells.…”

Facilitated glucose transporter protein type 1 (GLUT1) deficiency syndrome: impaired glucose transport into brain – a review

“…In patients without mutations, the GLUT1 Patients that do not fit the above criteria might carry secondary or tissue-specific GLUT1 defects, but classification of this group is difficult defect could well be secondary or acquired. Impaired GLUT1 function has been reported in association with toxins, seizure activity [13,14], trauma [12,66,67], infectious agents [27,48], and other insults to the brain [9].…”