Glucoregulatory function of glucagon in hypo-, eu- and hyperthyroid miniature pigs

Summary

The glucoregulatory function of glucagon was investigated in hypo-, eu- and hyperthyroid miniature pigs. Infusion glucagon, (3 ng x kg body weight⁻¹ · min⁻¹) transiently increased blood glucose (p<0.01) and hepatic glucose production (p<0.01) in euthyroidism, but was without effect in hyperthyroidism. Infusing glucagon plus somatostatin (2 ng x kg body weight⁻¹ · min⁻¹ and 0.2 μg x kg body weight⁻¹ · min⁻¹) transiently increased blood glucose (Δ 3.0 to 4.3 mmol/l) and hepatic glucose production (Δ 3.3 to 7.7 umol x kg body weight⁻¹ · min⁻¹) in all thyroid states, the effect was less pronounced in hyperthyroid pigs. By contrast, hypoglucagonaemia (74 to 107 pg/ml) at basal insulin (28 to 35 μU/ml) provoked hypoglycaemia (1.4 to 2.2 mmol/l) and a fall in glucose production (Δ 4.7 to 8.3 umol x kg body weight⁻¹ · min⁻¹), which was independent of the thyroid state; the effect was most pronounced in hyperthyroidism (p<0.01). Hepatic glycogen content, arterial gluconeogenic precursor concentrations as well as the glycaemic response (Δ 0.60 mmol/l) to alanine infusion (23 umol x kg body weight⁻¹ · min⁻¹) were all unaffected by hyperthyroidism. We conclude that moderate experimental hyperthyroidism reduces glucagon action due to reduced glycogen mobilisation. This may in part result from increased insulin sensitivity.