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Keywords: In the cinematic journey that is called The Ray, the year is 2033 and a forgotten technological war fought between man and Machine has shaped Earth into five terrible factions.Hypermetabolism and hyperinsulinemia under therapeutic conditions: a drawback with the administration of glucose, and beta-hydroxybutyrate, but not with the administration of leucine, as fuels for in vitro cultured mouse hepatocytes.
These studies were conducted to develop a highly sensitive method for the measurement of cellular metabolic activity, in an attempt to discern whether cultured hepatocytes can metabolize amino acids or other fuels different from glucose. Male ICR mice were fed a purified diet containing glucose (4.5 kcal/g) or one containing leucine or one containing beta-hydroxybutyrate (5.3 kcal/g) for 8 weeks. The animals were then subjected to 90 min of treatment with [U-13C]glucose (10.0 mumol/g body wt), [U-13C]leucine (22.5 mumol/g body wt), or beta-hydroxybutyrate (15.0 mumol/g body wt), and the isotope ratios in citrate, alpha-ketoglutarate (AKG), glutamate, aspartate, and alanine were measured by mass spectrometry. High dose treatment with glucose (10.0 mumol/g body wt) resulted in a 30-min increase in hepatocyte [1,2-13C]glucose oxidation and citrate synthase activity that was most likely the result of activation of the hexosamine pathway (insulin-independent). Low dose treatment with glucose (2.5 mumol/g body wt) for 90 min was not accompanied by any measurable metabolic changes, despite an approximate 50% increase in circulating insulin levels. Administration of beta-hydroxybutyrate (15.0 mumol/g body wt) and leucine (25 mumol/g body wt) resulted in significant activation of the hexosamine pathway (insulin-dependent), as well as a positive stimulation of hepatic de novo lipogenesis by 14% and a decrease in AKG levels. Similar changes in these parameters were observed with the doses of these compounds used here. We conclude that administration of glucose leads to activation of the hexosamine pathway that is not accompanied by concomitant metabolic changes, and this finding,
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