PERTURBATIONS OF GLUCOSE-METABOLISM ASSOCIATED WITH HIV-INFECTION IN HUMAN INTESTINAL EPITHELIAL-CELLS - A MULTINUCLEAR MAGNETIC-RESONANCE SPECTROSCOPY STUDY

Objective: To analyse the effect of HIV-1 infection on the glucose met abolism of human intestinal epithelial cells. Methods: HT-29 cells wer e infected with HIV-1(NDK) and studied 3 weeks (acutely infected cells ) or 9 months (chronically infected cells) post-infection. Perchloric acid extracts were analysed by high-resolution H-1, P-31 and C-13 nucl ear magnetic resonance spectroscopy. Metabolite concentrations and spe cific C-13 enrichments were quantified for chronically infected, acute ly infected and control cells grown in Dulbecco's modified Eagle's med ium containing natural-abundance or l-C-13-enriched glucose to determi ne significant differences between infected and non-infected cells. Re sults: Chronically HIV-infected cells showed alterations in glycerol-3 -phosphate (+40%), fructose-l,6-diphosphate (-66%), uridine diphosphat e glucuronic acid (-33%), lactate (+75%) and [l-(13)Clglucose (+181%) levels, and in specific lactate 3-C-13 enrichment (+19%) when compared with controls. Acutely infected cells exhibited decreased fructose-l, 6-diphosphate (-58%) and increased nicotinamide adenine dinucleotide ( +33%) levels relative to controls. Conclusion: HIV-1 infection results in a disturbance of glycolytic and oxidative activities in human inte stinal epithelial cells. This finding supports the concept that HIV-1 may directly impair some metabolic functions of the intestinal epithel ium, and that it can be considered a potential aetiological agent for HIV-associated enteropathy.