Glucagon Does Not Modulate the Alterations in T3 Metabolism Consequent to Dietary Manipulation and Diabetes
Authors: Gavin Laurence A , Moeller Marie 
Published: September 2013

Low serum T3 levels and hyperglucagonemia are characteristic features of a number of catabolic states such as fasting and uncontrolled diabetes. The present study was performed to elucidate the relationship between this hyperglucagonemia and T3 metabolism. Serum glucagon and T3 and hepatic T4-5'-deiodinase activity (T4 → T3) were examined in groups of rats (T4-treated) fed (chow versus carbohydrate), fasted, or diabetic (streptozotocin 100 mg/kg i.p.) for 48–72 h.
In the carbohydrate-fed (20% glucose in H2O ad libitum) group the mean serum T3 concentration and mean hepatic T4-5'-deiodinase activity were significantly higher (P &lt; 0.01) and the mean serum glucagon level significantly lower (P &lt; 0.05) than the respective means in the chow-fed control group. The mean serum T3 concentration was significantly less (P &lt; 0.05) in both the fasted (72 h) and diabetic (72 h) groups compared with the control mean, whereas the mean serum glucagon values were similar to the chow-fed group. The mean hepatic T4-5'-deiodinase activity was low in the diabetic group (P &lt; 0.05) but similar in the fasted group compared with the chow-fed control. A significant inverse correlation (r = −0.9; P &lt; 0.001) was noted between these alterations in serum T3, hepatic T4-5'-deiodinase activity, and serum glucagon, suggesting that glucagon could be a modulator of T3 metabolism.
Hyperglucagonemia was induced in the glucose-fed group with a continuous glucagon infusion for 48 h (0.15 μG/min s. c.). Both the mean serum glucagon (395 ± 66 pg/ml) and glucose concentrations (152 ± 5 mg/dl) were significantly higher (P &lt; 0.01) in the glu-cagon-treated group compared with the respective mean values (glucagon = 147 ± 8 pg/ml, glucose = 126 ± 2 mg/dl) in the control group. Despite this hy- perglucagonemia there was no change in T3 metabolism; serum T3 values and enzyme activity were similar in both groups. Hypoglucagonemia was induced in both the fasted (72 h) and diabetic (72 h) groups by a continuous somatostatin infusion for 72 h (0.8 μg/kg/ min s.c). The mean serum glucagon was reduced from 84 ± 7 to 60 ± 7 pg/ml by somatostatin in the fasted group (P &lt; 0.05) and from 137 ± 12 to 102 ± 5 pg/ml by somatostatin in the diabetic group (P &lt; 0.05). Despite these significant reductions in serum glucagon in both the fasted and diabetic groups, no increase was noted in either serum T3 or hepatic T4-5'-deiodinase activity.
However, it was noted that the hyperglucagonemia consequent to the glucagon infusion in the glucose-fed group was associated with a relative excess of insulin. The mean serum molar ratio of insulin to glucagon was 6.9 ± 2.3 in the glucagon-treated group compared with 3.3 ± 0.3 in the glucose-fed control group. Thus, it seemed possible that the insulin excess could have masked a possible glucagon inhibitory effect on T4-5'-deiodinase activity. A coinfusion (48 h) of glucagon and somatostatin was used to induce a significant reduction (P &lt; 0.05) in the molar ratio of insulin to glucagon (1.5 ± 0.6) in the glucose-fed group. However, no reduction occurred in either serum T3 or hepatic T4-5-deiodinase activity during this hyperglucagonemic state.
Thus, glucagon does not modulate T3 metabolism and the low T3 state of either fasting or diabetes is not related to the associated hyperglucagonemia.