Kinetic analysis of thyroid hormone action on glucose metabolism in man.
Thyroid hormone action on insulin's effect on glucose kinetics was investigated with the use of a physiological three compartment model. In six healthy volunteers before and after 14 days of thyroxine treatment (300 micrograms/day), a bolus of [3-H3]glucose was injected and the time course of plasma radioactivity was followed closely for 150 min. Then a hyperinsulinemic (1 mU.min-1.kg-1) and euglycemic clamp was started, and euglycemia was maintained for another 250 min. A second bolus of the tracer was then given at 240 min, and the plasma radioactivity was followed for 160 min. Insulin stimulated basal plasma glucose clearance fourfold (p < 0.001) and completely suppressed basal hepatic glucose production (p < 0.001). Concomitantly, the total distribution volume of glucose was increased by 19% (p < 0.05); this change was accompanied by about 50% expansion of the slowly exchanging glucose pool (putatively representing the insulin-dependent compartment). Thyroxine treatment increased plasma triiodothyronine by about 20% (0.1 > p > 0.05) but did not affect basal glucose turnover, insulin-stimulated plasma glucose clearance or the insulin-induced suppression of endogenous glucose output. However, thyroxine treatment blunted the insulin-induced increases in total distribution volume and the slowly exchanging pool of glucose (p = NS vs the basal state). We conclude that minor changes in plasma triiodothyronine (such as occur during overfeeding) do not interfere with the ability of insulin to stimulate the rate of disappearance of glucose or suppress endogenous glucose release; however, our data suggest that they induce finer changes in glucose kinetics, possibly reflecting acceleration or intracellular glucose degradation.
Müller
M J
MJ
Division d'Endocrinologie, Hôpital Cantonal Universitaire de Genève, Switzerland.
Reynard
C A
CA
Burger
A G
AG
Toffolo
G
G
Cobelli
C
C
Ferrannini
E
E
D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D005947:Glucose / Q000378:metabolism* / Q000494:pharmacology; D015309:Glucose Clamp Technique; D006801:Humans; D007328:Insulin / Q000097:blood / Q000494:pharmacology; D008297:Male; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood / Q000494:pharmacology*; D013997:Time Factors; D014284:Triiodothyronine / Q000097:blood / Q000494:pharmacology; D014316:Tritium
D001786:Blood Glucose; D007328:Insulin; D014284:Triiodothyronine; D014316:Tritium; D013972:Thyrotropin; D005947:Glucose; D013974:Thyroxine