Effects of glucocorticoids on glutamine metabolism in visceral organs.
The effect of dexamethasone on interorgan glutamine exchange was studied in order to gain further understanding of the changes in nitrogen metabolism that occur following catabolic illness. In addition to studying glutamine, which transports as much as 40% of whole blood amino acid nitrogen, we determined the fluxes of glutamate, alanine, and glucose across the gastrointestinal tract, liver, and kidneys in 25 awake, chronically-catheterized dogs. Studies were performed during a control period and after dexamethasone (DEX) treatment (0.44 mg/kg X day) for two (DEX 2) and nine (DEX 9) days. Following dexamethasone treatment, arterial concentration of glutamine and glutamate fell, while alanine and glucose levels increased. Glutamine uptake by the intestine doubled with DEX (control 0.96 +/- 0.13 mumol/kg X min v 2.23 +/- 0.24 on DEX 2, P less than 0.001, and 1.59 +/- 0.20 on DEX 9, P less than 0.05). Alanine was produced by the intestine in controls (1.96 +/- 0.30 mumol/kg X minute), and release rate increased twofold on DEX 2 (4.10 +/- 0.66, P less than 0.01). The liver remained in balance for glutamine during both the control state and following DEX treatment, while renal glutamine uptake and renal glucose release were significantly increased after DEX. Glucocorticoids influence amino acid and glucose metabolism in the gastrointestinal tract, liver, and kidneys. The marked increase in glutamine extraction and alanine production by the intestine in response to glucocorticoids suggests that altered gastrointestinal amino acid metabolism may contribute to both the low glutamine levels and the accelerated gluconeogenesis that occur during catabolic illness.
D000409:Alanine / Q000097:blood / Q000378:metabolism; D000596:Amino Acids / Q000097:blood; D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology*; D004285:Dogs; D005260:Female; D005971:Glutamates / Q000097:blood / Q000378:metabolism; D005973:Glutamine / Q000097:blood / Q000378:metabolism*; D007408:Intestinal Absorption / Q000187:drug effects; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000098:blood supply; D007668:Kidney / Q000098:blood supply / Q000378:metabolism*; D008099:Liver / Q000098:blood supply / Q000378:metabolism*; D008297:Male; D012039:Regional Blood Flow
D000596:Amino Acids; D005971:Glutamates; D005973:Glutamine; D003907:Dexamethasone; D000409:Alanine