Differential Effects of Insulin-like Growth Factor-1 on Neonatal Canine Gene Expression

Abstract

To determine the effects of insulin-like growth factor-1 (IGF-1) and amylin on glucose homeostasisin vivoin newborn dogs, euglycemic hyper-IGF-1 clamps and hypoglycemic hyper-IGF-1 clamps were performed in newborn dogs. Northern blotting and radioimmunoassays were used to study the effects of the infused IGF-1 and/or hypoglycemia on the mRNA expression of the genes for phosphoenolpyruvate carboxykinase (PEPCK) and on the expression of the amylin gene in newborn dogs. Our results were that (1) Infused IGF-1 (plasma IGF-1 ≥1000 ng/ml) rapidly lowered the plasma glucose level, and 120 ± 38 mg glucose/pup was co-infused during a 105-min clamp to maintain the plasma glucose at the basal level. (2) The infused IGF-1 rapidly reduced the liver cytosolic mRNA for the PEPCK gene to an almost undetectable level. (3) Hyper-IGF-1 had no effect on mRNA level of the amylin gene in pancreas, 106.7 ± 14.2% vs 100.0 ± 5.9% (controls), or on plasma amylin concentration, 56.0 ± 5.7 pg/ml vs 52.1 ± 5.7 pg/ml (basal). (4) The amylin mRNA level, 127.8 ± 3.9% vs 100.0 ± 5.9% (controls) (P= 0.017), and the plasma amylin concentration, 132.3 ± 18.3 pg/ml vs 110.0 ± 10.8 pg/ml (controls) (P= 0.371), showed a parallel stimulation by hypoglycemia in the presence of hyper-IGF-1. We concluded that (1) IGF-1 acutely suppressed cytosolic PEPCK gene expression in liver of newborn dogs. (2) IGF-1 does not effect the expression of the pancreatic amylin gene. (3) Amylin may be involved in glucose homeostasis in newborn dogs and may play a role as a counterregulatory factor during the neonatal period. Unsuppressed amylin production may contribute to neonatal hyperglycemia.