High-fructose diet stimulates hepatic de novo lipogenesis (DNL) and causes hypertriglyceridemia and insulin resistance in rodents. Fructose-induced insulin resistance may be secondary to alterations of lipid metabolism. In contrast, fish oil supplementation decreases triglycerides and may improve insulin resistance. Therefore, we studied the effect of high-fructose diet and fish oil on DNL and VLDL triglycerides and their impact on insulin resistance. Seven normal men were studied on four occasions: after fish oil (7.2 g/day) for 28 days; a 6-day high-fructose diet (corresponding to an extra 25% of total calories); fish oil plus high-fructose diet; and control conditions. Following each condition, fasting fractional DNL and endogenous glucose production (EGP) were evaluated using [1-13 C]sodium acetate and 6,6-2 H 2 glucose and a two-step hyperinsulinemic-euglycemic clamp was performed to assess insulin sensitivity. High-fructose diet significantly increased fasting glycemia (7 ؎ 2%), triglycerides (79 ؎ 22%), fractional DNL (sixfold), and EGP (14 ؎ 3%, all P < 0.05). It also impaired insulin-induced suppression of adipose tissue lipolysis and EGP (P < 0.05) but had no effect on wholebody insulin-mediated glucose disposal. Fish oil significantly decreased triglycerides (37%, P < 0.05) after high-fructose diet compared with high-fructose diet without fish oil and tended to reduce DNL but had no other significant effect. In conclusion, high-fructose diet induced dyslipidemia and hepatic and adipose tissue insulin resistance. Fish oil reversed dyslipidemia but not insulin resistance. Diabetes

The use of stable, isotopically labeled compounds in controlled exposure experiments at environmentally relevant levels allows for the distinguishing of urinary metabolites associated with known exposure from background levels generally present in the urine. Exposures of volunteers to (13)C-benzene for 2 h at 40+/-10 p.p.b. were conducted after obtaining informed consent, and urinary phenol, catechol, hydroquinone and trans,trans- muconic acid were measured. Each isotopically labeled urinary metabolite was determined in the presence of significantly higher concentrations of the unlabeled metabolite. Following exposure, free and acid hydrolyzed phenol, acid hydrolyzed catechol and hydroquinone, and free trans,trans-muconic acid were determined by GC/MS. The percentage of trans,trans-muconic acid excreted was higher than reported following exposure at occupational levels. The use of isotopically labeled compounds has the potential to investigate the metabolism of common environmental contaminants for validation of toxicokinetic models and improve risk extrapolation from high concentration occupational exposures and animal studies to environmentally relevant pollutant levels.

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In the absence of HIV infection, changes in adipose tissue and lipid levels, HIV protease inhibitor therapy increases fasting glucose levels,suggestive of hepatic insulin resistance. After 4 weeks of indinavir treatment in nine HIV-negative healthy men, fasting glucose production and glycogenolysis were significantly increased. During the euglycemic hyperinsulinemic clamp, indinavir blunted the ability of insulin to suppress glucose production. Therefore, indinavir worsens hepatic insulin sensitivity, increasing endogenous glucose production.