Glucagon kinetics in growing rats fed different levels of protein and/or energy

The present work was carried out to evaluate the kinetic parameters of glucagon in growing rats divided into three groups: T, H and E. Group T (Control group) was fed a control diet (crude protein: 11.8%). Groups H and E received a high protein diet (crude protein: 19%) distributed in either equal (Group H) or restricted amounts (Group E) with respect to the control. Thus, the main characteristic of Group H was the high level of protein intake (+ 68%) when Group E rats underwent a moderate increase in protein intake but a striking caloric deprivation (-25%). In all cases, the animals were fed a meal every 4 hours. The kinetic parameters of glucagon metabolism were estimated from the plasma disappearance curves of 125I-glucagon for five minutes following a pulse injection of purified 125I-glucagon (1 muCi, about 3.8 ng/100 g BW). Plasma 125I-glucagon was measured after gel filtration of plasma on Biogel P-10. Tissue radioactivity (mainly liver and kidneys) was recorded seven minutes after 125I-glucagon injection. The results showed that the plasma 125I-glucagon level was higher in Group H than in the other groups 1 min after the injection. At all other times (2, 3.5 and 5 min) it was similar in all groups. 125I-glucagon was rapidly cleared from plasma and rapidly taken up by the liver and kidneys. In the 3 experimental groups, mean half-life and metabolic clearance rate were estimated to be 2 min and 6 ml/min/100 g BW, respectively. Excess protein intake resulted in a reduction in the apparent initial distribution volume of 125I-glucagon without modifying significantly its turn-over rate and metabolic clearance rate. Kidneys and liver (6% BW) accounted for about 20% of the 125I-glucagon uptake by tissues 7 min after injection. Group H kidneys and liver were more labelled than in other groups. These results suggest that increased protein intake (without further caloric deprivation) can induce some changes in glucagon metabolism which could partially contribute to the increase in glucagonemia usually observed in animals fed high protein diets.