title: T4 uptake into the perfused rat liver and liver T4 uptake in humans are inhibited by fructose.
abstract: Recently, we described a two-pool model for 3,5,3'-triiodothyronine uptake and metabolism in the isolated perfused rat liver. Here, we applied this model to investigate transmembrane thyroxine (T4) transport and its possible ATP dependence in vivo. These studies are performed in perfused rat livers during perfusion with or without fructose in the medium, as it has been shown that intracellular ATP is decreased after fructose loading. Furthermore, we studied serum T4 tracer disappearance curves in four human subjects before and after intravenous fructose loading. In the perfused rat liver, we found a decrease in liver ATP concentration and a decrease in medium T4 disappearance and T4 uptake in the liver pool after fructose. Furthermore, it was shown that, when corrected for differences in the medium free hormone concentration, only transport to the metabolizing liver pool was decreased after fructose perfusion, whereas uptake in the nonmetabolizing pool was unaffected. Disposal, corrected for differences in transport into the metabolizing pool, was also not affected after fructose. In the human studies, intravenous fructose administration induced a rise in serum lactic acid and uric acid, indicating a decrease in liver ATP. This was observed concomitant with a decrease in serum tracer T4 disappearance during the first 3 h after fructose administration. These results suggest ATP dependence of transport of iodothyronines into the liver in vivo and show that, in the rat liver and in humans, uptake of T4 may be regulated by intracellular energy stores; in this way the tissue uptake process may affect intracellular metabolism and bioavailability of thyroid hormone.
authors.affiliation: Department of Internal Medicine III, Erasmus University Rotterdam, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: De Jong
authors.forename: R
authors.initials: R
authors.lastname: Docter
authors.forename: B F
authors.initials: BF
authors.lastname: Bernard
authors.forename: J T
authors.initials: JT
authors.lastname: van der Heijden
authors.forename: H
authors.initials: H
authors.lastname: van Toor
authors.forename: E P
authors.initials: EP
authors.lastname: Krenning
authors.forename: G
authors.initials: G
authors.lastname: Hennemann
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000328:Adult; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D005260:Female; D005632:Fructose / Q000494:pharmacology*; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D007773:Lactates / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008433:Mathematics; D008657:Metabolic Clearance Rate; D008954:Models, Biological; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood / Q000378:metabolism*; D013997:Time Factors; D014284:Triiodothyronine / Q000097:blood; D014285:Triiodothyronine, Reverse / Q000097:blood; D014527:Uric Acid / Q000097:blood
chemical_list: D007773:Lactates; D014284:Triiodothyronine; D014527:Uric Acid; D005632:Fructose; D014285:Triiodothyronine, Reverse; D000255:Adenosine Triphosphate; D013972:Thyrotropin; D005947:Glucose; D013974:Thyroxine