To study the effects of insulin on leucine turnover during fasting, acute insulin deficiency was induced by the simultaneous infusion of somatostatin and glucagon in conscious dogs fasted 18 h (N = 10) and 48 h (N = 11). Insulin levels during the basal period (before hormone perturbation) were similar in both groups of dogs (12 ± 3 versus 10 ± 3 μU/ml, respectively). Glucagon levels were similar in the two groups (94 ± 9 versus 106 ± 19 pg/ml). Leucine levels rose from 118 ± 9 jimol/L to 155 ± 12 fimol/L as fasting progressed (P < 0.005). Its rate of appearance also increased by 30% (P < 0.005) from 3.4 ± 0.3 to 4.3 ± 0.4 μmol/kg/min (P < 0.005), while its clearance remained unchanged. Acute insulin deficiency caused an increase in leucine levels in both 18-h and 48-h-fasted dogs by 55% (to 181 ± 10 μnol/L) and 45% (to 225 ± 20 μmol/L), respectively (P < 0.005). However, while the rate of appearance of leucine remained unchanged in dogs fasted overnight, it rose to 5.1 ± 0.3 μmol/kg/min (P < 0.01) in those fasted 48 h. The metabolic clearance rate fell in both groups, although this drop was twice as great in the 18-h group (from 28 ± 3 to 17 ± 3 ml/kg/min, P < 0.005) as in the 48-h group (from 28 ± 3 to 23 ± 2 ml/kg/min, P < 0.005).
We conclude that insulin has disparate effects on protein turnover as fasting becomes more prolonged. Its acute absence results in enhanced proteolysis in the 2-day-fasted, but not in the overnight-fasted dog. These data suggest that the response of protein turnover to fasting is quite complex and involves more than the effects of changing insulin concentrations.
