Insulin-like growth factor-1 (IGF-1) exerts insulin-like effects on glucose homeostasis. Amylin is a newly discovered pancreatic hormone which may impair insulin action. IGF-1 has been reported to reduce plasma amylin level in adult rats. In the present study, the effects of IGF-1 on the expression of the liver phosphoenolpyruvate carboxykinase (PEPCK) gene and the pancreatic amylin gene in newborn dogs were tested to determine the effects on neonatal glucose metabolism by IGF-1. After C-section delivery, euglycemic hyper-IGF-1 clamps(IGF-1 infusion rate: 10 μg/kg/min) were performed in newborn dogs (N=3). Total RNAs were isolated from frozen liver and pancreas. Northern blottings were performed using a rat PEPCK cDNA probe and a dog amylin cDNA probe to measure the mRNA levels of the PEPCK and amylin genes. The mRNA bands were quantitatively analyzed by a densitometer. The plasma concentration of amylin and IGF-1 were analyzed by radioimmunoassay. Results: 1) After the clamps, the plasma IGF-1 concentration was sharply increased to 2,822.2± 539.5 ng/ml from 128.3 ± 15.4 ng/ml (basal), whereas the plasma glucose level (143.0 ± 13.7 mg/dl) was kept at basal level(138.3 ± 18.1) by a variable infusion of glucose; 2) IGF-1 lowered the liver PEPCK mRNA level (75.1 ± 2.8) by 45.7%, compared to control(138.4 ± 41.2%); 3) IGF-1 inhibited neither amylin mRNA level (106.7± 14.2%) compared with the basal (100.0 ± 5.9%) nor the plasma amylin level (56.6 ± 3.8 pg/ml) compared to the basal (60.3 ± 5.5 pg/ml). The results suggest that IGF-1 may effectively suppress neonatal gluconeogenesis but that the unaffected amylin expression in newborn dogs by IGF-1 may be a counterregulatory factor for inducing insulin resistance in neonatal mammalians.