Glucose regulation of hydroperoxide metabolism in rat intestinal cells. Stimulation of reduced nicotinamide adenine dinucleotide phosphate supply.
The regulation of intestinal metabolism of t-butylhydroperoxide by glucose was examined in isolated enterocytes from proximal rat intestine. The basal rate of hydroperoxide elimination in control cells was 0.57 +/- 0.05 nmol/min per 10(6) cells, and was increased threefold by 10 mM exogenous glucose (1.74 +/- 0.14 nmol/min per 10(6) cells). Concurrently, cellular NADPH levels increased threefold (1.62 +/- 0.40 nmol/10(6) cells vs 0.57 +/- 0.14 nmol/10(6) cells in controls). The glucose effect was blocked by 6-aminonicotinamide and by 1,3-bis-(2-chloroethyl) 1-nitrosourea, consistent with glucose stimulation of NADPH production by the pentose phosphate shunt, and of NADPH utilization for glutathione disulfide reduction. The NADPH supply rate was quantified by controlled infusions of diamide, a thiol oxidant. At diamide infusion of 0.05 nmol/min per 10(6) cells, GSH and protein thiols in control cells were decreased significantly, consistent with a limited capacity for glutathione disulfide reduction. With glucose, cell GSH and protein thiols were preserved at a 10-fold higher diamide infusion which was reversed by 6-aminonicotinamide, supporting the view that glucose promotes glutathione disulfide reduction by increased NADPH supply. Collectively, the results demonstrate that intestinal metabolism of hydroperoxides subscribes to regulation by glucose availability. This responsiveness to glucose suggests that nutrient availability would be an important contributing factor in the detoxication of toxic hydroperoxides by the small intestine.
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Department of Physiology and Biophysics, Louisiana State University Medical Center, Shreveport 71130.
Rhoads
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D015120:6-Aminonicotinamide / Q000494:pharmacology; D000818:Animals; D002330:Carmustine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D008658:Inactivation, Metabolic; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000166:cytology / Q000187:drug effects; D008297:Male; D009249:NADP / Q000378:metabolism; D010084:Oxidation-Reduction; D010427:Pentose Phosphate Pathway; D010545:Peroxides / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*; D020122:tert-Butylhydroperoxide
D010545:Peroxides; D017382:Reactive Oxygen Species; D015120:6-Aminonicotinamide; D009249:NADP; D020122:tert-Butylhydroperoxide; D005978:Glutathione; D005947:Glucose; D002330:Carmustine