Hepatic carbon flux after re-feeding. Hyperthyroidism blocks glycogen synthesis and the suppression of glucose output observed in response to carbohydrate re-feeding.
1. The work investigated hepatic glycogen synthesis and glucose output after the intragastric administration of glucose or glycerol or the provision of chow ad libitum to 48 h-starved euthyroid or hyperthyroid rats. 2. After glucose administration, glycogen synthesis via the indirect pathway [Newgard, Hirsch, Foster & McGarry (1983) J. Biol. Chem. 258, 8046-8052] occurred concomitantly with reversal of glucose flux across the liver and re-activation of pyruvate kinase in the euthyroid controls. Glycogen synthesis was decreased and net glucose output continued in the hyperthyroid rats, but normal re-activation of pyruvate kinase was observed. 3. Use of 3-mercaptopicolinate indicated that the glucose released from liver of hyperthyroid rats was synthesized from substrates metabolized via the gluconeogenic pathway. 4. Hepatic glycogen synthesis was also impaired in hyperthyroid rats after administration of glycerol or chow. Measurement of portal-minus-hepatovenous concentration differences and arterial glucose concentrations after the administration of glycerol in combination with 3-mercaptopicolinate indicated that flux from triose phosphate to glucose 6-phosphate was not decreased. 5. Inhibited glycogen synthesis after chow re-feeding was associated with accelerated re-activation of hepatic pyruvate dehydrogenase complex in the hyperthyroid rats. 6. The results indicate three distinct and independent actions of hyperthyroidism after re-feeding: (i) it inhibits the reversal of glucose flux across the liver normally observed in response to carbohydrate; (ii) it affects glycogen deposition at a site distal to glucose 6-phosphate; (iii) it allows more rapid re-activation of liver pyruvate dehydrogenase complex in response to a mixed diet.
Department of Chemical Pathology, London Hospital Medical College, U.K.
M J
MJ
Holness
M C
MC
Sugden
D000818:Animals; D004040:Dietary Carbohydrates / Q000494:pharmacology*; D005260:Female; D005502:Food; D005947:Glucose / Q000378:metabolism* / Q000494:pharmacology; D019298:Glucose-6-Phosphate; D005958:Glucosephosphates / Q000378:metabolism; D006980:Hyperthyroidism / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008112:Liver Glycogen / Q000096:biosynthesis*; D051381:Rats; D011919:Rats, Inbred Strains; D013217:Starvation / Q000378:metabolism; D014284:Triiodothyronine / Q000494:pharmacology
D004040:Dietary Carbohydrates; D005958:Glucosephosphates; D008112:Liver Glycogen; D014284:Triiodothyronine; D019298:Glucose-6-Phosphate; D005947:Glucose