title: Hepatic glucose production and splanchnic glucose exchange in hyperthyroidism.
abstract: Hepatic glucose production (HGP) and net splanchnic glucose balance (NSGB) were simultaneously determined in the basal state in 8 hyperthyroid patients and 10 normal subjects using iv infusion of [3H]3-glucose and the hepatic venous catheter technique. Splanchnic glucose uptake (SGU) was calculated as the difference between the HGP and NSGB. SGU was also measured by determining the splanchnic extraction ratio of [3H]3-glucose across the splanchnic bed. In 5 hyperthyroid patients and 5 normal subjects a renal vein was also catheterized in the basal state. The influence of increased endogenous insulin secretion [stimulated by a low rate iv infusion of glucose (2 mg/kg . min)] on splanchnic and hepatic glucose exchange was also examined. Basal HGP (measured with [3H]3-glucose) was increased by 20% in the hyperthyroid patients [14.2 +/- 0.6 (SEM) mumol/kg . min] as compared to normal subjects (11.9 +/- 0.6, P less than 0.02). In marked contrast, NSGB output was slightly but not significantly decreased in the hyperthyroid group. SGU in the hyperthyroid patients, as determined with both techniques, was more than 2-fold higher than in the normal group (P less than 0.02-P less than 0.005). Splanchnic uptake of gluconeogenic precursors (lactate, pyruvate, glycerol) was increased by 20-120% in the patient group. During iv infusion of glucose, plasma insulin levels increased more in the hyperthyroid group (66% vs. 37%, P less than 0.05). Nevertheless, HGP and NSGB were less markedly suppressed in the patients as compared to the normal subjects (P less than 0.01), whereas the augmented SGU in the hyperthyroid patients reverted to normal. Splanchnic uptake of gluconeogenic precursors was unchanged in both groups. No net renal glucose production could be demonstrated in either group in the basal state. We conclude that in hyperthyroidism, increased HGP occurs in the face of an unchanged or slightly reduced rate of net glucose delivery to extrasplanchnic tissue. This discrepancy can be ascribed to augmented splanchnic uptake of glucose. These findings raise the possibility of futile cycling of glucose in the liver as a mechanism of increased oxygen consumption in hyperthyroidism. The data also demonstrate a diminished inhibitory effect of endogenous insulin on splanchnic glucose production, suggesting the presence of hepatic resistance to insulin in hyperthyroidism.
mesh_terms: D000328:Adult; D001158:Arteries; D001786:Blood Glucose / Q000378:metabolism; D004837:Epinephrine / Q000097:blood; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D006980:Hyperthyroidism / Q000378:metabolism*; D007328:Insulin / Q000097:blood; D007700:Kinetics; D007773:Lactates / Q000097:blood; D008099:Liver / Q000378:metabolism*; D008875:Middle Aged; D009638:Norepinephrine / Q000097:blood; D011773:Pyruvates / Q000097:blood; D012016:Reference Values; D013152:Splanchnic Circulation; D014316:Tritium
chemical_list: D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D007773:Lactates; D011773:Pyruvates; D014316:Tritium; D005947:Glucose; D009638:Norepinephrine; D004837:Epinephrine