Insulin's effect on Leucine turnover changes during early fasting in the conscious dog

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 microU/ml, respectively). Glucagon levels were similar in the two groups (94 +/- 9 versus 106 +/- 19 pg/ml). Leucine levels rose from 118 +/- 9 mumol/L to 155 +/- 12 mumol/L as fasting progressed (P less than 0.005). Its rate of appearance also increased by 30% (P less than 0.005) from 3.4 +/- 0.3 to 4.3 +/- 0.4 mumol/kg/min (P less than 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 mumol/L) and 45% (to 225 +/- 20 mumol/L), respectively (P less than 0.005). However, while the rate of appearance of leucine remained unchanged in dogs fasted overnight, it rose to 5.1 +/- 0.3 mumol/kg/min (P less than 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 less than 0.005) as in the 48-h group (from 28 +/- 3 to 23 +/- 2 ml/kg/min, P less than 0.005). We conclude that insulin has disparate effects on protein turnover as fasting becomes more prolonged.(ABSTRACT TRUNCATED AT 250 WORDS)