title: Use of 3H and 14C doubly labeled glucose and amino acids in the study of hormonal regulation of gluconeogenesis in rats.
abstract: Double isotope procedures (3H and 14C) were used in vivo to investigate a) slow long-term gluconeogenic actions of adrenal glucocorticoids, and b) rapid stimulation of gluconeogenesis by glucagon. [U-14C,6-3H]Glucose was administered to normal and adrenalectomized rats. No effect was observed on the [6-3H]glucose half-life suggesting the dicarboxylic acid shuttle is unaffected by adrenalectomy; the Cori cycle is also not influenced. Loads of [14C]aspartate, [14C]glutamate, or [14C]alanine were given to normal and adrenalectomized rats. Simultaneously, in vivo transaminase activity was studied by measuring the appearance of 3H2O in body water after administration of [2-3H]aspartate, [2-3H]glutamate, or [2-3H]alanine, Adrenalectomy has no influence on the incorporation of glutamate or aspartate into glucose or on their in vivo transaminases. Diminution of incorporation of [14C]alanine into glucose and alanine transaminase activities occurs only when rats are given unphysiological loads. These studies support the contention that glucocorticoid rate-limiting actions occur in extrahepatic tissues to produce an increased flow of glucose precursors to the liver. [U-14C,3-3H]Glucose was used to investigate the effect of glucagon on the hepatic fructose-6-phosphate (F-6-P) cycle. Glucagon administration resulted in a rapid drop in the 3H/14C ratio of circulating glucose, suggesting an increase in F-6-P recycling caused by activation of FDPase with little or no decrease in phosphofructokinase. Such a change would direct substrate flux toward gluconeogenesis.
mesh_terms: D000315:Adrenalectomy; D000409:Alanine / Q000378:metabolism; D000410:Alanine Transaminase / Q000378:metabolism; D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D001219:Aspartate Aminotransferases / Q000378:metabolism; D001224:Aspartic Acid / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D002250:Carbon Radioisotopes; D003920:Diabetes Mellitus / Q000378:metabolism; D006597:Fructose-Bisphosphatase / Q000378:metabolism; D005934:Glucagon / Q000494:pharmacology*; D005943:Gluconeogenesis / Q000187:drug effects*; D005947:Glucose / Q000378:metabolism*; D005971:Glutamates / Q000378:metabolism; D008297:Male; D010732:Phosphofructokinase-1 / Q000378:metabolism; D051381:Rats; D013268:Stimulation, Chemical; D013311:Streptozocin; D014316:Tritium
chemical_list: D000596:Amino Acids; D001786:Blood Glucose; D002250:Carbon Radioisotopes; D005971:Glutamates; D014316:Tritium; D001224:Aspartic Acid; D013311:Streptozocin; D005934:Glucagon; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D010732:Phosphofructokinase-1; D006597:Fructose-Bisphosphatase; D005947:Glucose; D000409:Alanine