Fasting and postabsorptive hepatic glucose and insulin metabolism in hyperthyroidism

Abstract

The effect of thyroid hormone excess on hepatic glucose balances and fractional hepatic extraction of insulin and glucagon was examined in six conscious dogs with catheters in the portal vein, hepatic vein, and femoral artery and Doppler flow probes on the portal vein and hepatic artery. An oral glucose tolerance test was performed before and after the animals were made hyperthyroid by intramuscular thyroxine administration (100 micrograms.kg-1.day-1) for 10 days. In the basal state and after oral glucose, insulin and glucagon levels in the three vessels and the basal fractional hepatic extraction of insulin and glucagon were not significantly modified by thyroid hormone. These results suggest that in short-term thyrotoxicosis insulin secretion is not impaired, and the rise in fasting plasma glucose and increased hepatic glucose production could reflect hepatic insulin resistance, increased availability of precursors for gluconeogenesis, or increased glycogenolysis. Hyperthyroidism significantly increased basal flows in the portal vein (14.7 +/- 0.6 vs. 12.9 +/- 0.5 ml.kg-1.min-1), the hepatic artery (4.8 +/- 0.3 vs. 3.9 +/- 0.2 ml.kg-1.min-1) and vein (19.6 +/- 0.7 vs. 16.9 +/- 0.4 ml.kg-1.min-1), the fasting plasma glucose concentration (104 +/- 3 vs. 92 +/- 2 mg/dl), and basal hepatic glucose output (2.1 +/- 0.2 vs. 1.5 +/- 0.2 mg.kg-1.min-1). It did not alter the nonhepatic splanchnic uptake of glucose, the percent of orally administered glucose that appeared in the portal vein (47 +/- 2 vs. 45 +/- 11%), the percent of hepatic uptake of glucose (59 +/- 11 vs. 74 +/- 22%), or the shape of the glucose tolerance test.

Thyroid hormone action in metabolic regulation

“…Animal studies have revealed that hyperthyroid animals develop elevated plasma glucose and insulin levels, due to increased hepatic glucose production including increased gluconeogenesis and glycogenolysis (Raboudi et al, 1989), and decreased glucose clearance and disposal. In human patients with Grave's hyperthyroidism, glucose tolerance is impaired (Randin et al, 1985).…”

Prevalence of thyroid dysfunction in patients with Type 2 diabetes mellitus and its correlation with insulin resistance and serum markers for autoimmune thyroiditis

“…While Thyroid hormones oppose the action of insulin and stimulate hepatic gluconeogenesis and glycogenolysis 12,13 they upregulate the expression of genes such as GLUT-4 and phosphoglycerate kinase involved in glucose transport and glycolysis respectively, thus acting synergistically with insulin facilititating glucose disposal and peripheral utilisation. 14,15 In hypothyroidism, glucose homeostasis is also affected although its clinical impact is less obvious.…”

The Pecularities of Correlation Between Insulin Resistance, Carbohydrate and Lipid Metabolism Indices in Patients With Graves’disease

“…Functional condition of thyroid was evaluated by determining the basal serum concentrations of TSH, FT 4 and FT 3 of patients, using enzyme-linked immunosorbent assay (ELIZA) with the help of test-system of company Roche Diagnostics (Switzerland) on automatic analyzer Cobas 6000 (e 601 module).…”

“…By "insulin resistance" (IR) we traditionally mean the altered tissue response to endogenous insulin, that is manifested by impaired glucose uptake in the adipose tissue and skeletal muscles, as well as suppression of hepatic gluconeogenesis [4]. Recent studies show that we can recognize IR not only in the pathogenesis of type 2 diabetes mellitus but also in many other pathological conditions, such as polycystic ovary syndrome, arterial hypertension, atherosclerosis, non-alcoholic steatohepatitis, etc.…”