DIFFERENTIAL-EFFECTS OF INSULIN-LIKE GROWTH-FACTOR-I ON NEONATAL CANINE GENE-EXPRESSION

To determine the effects of insulin-like growth factor-1 (IGF-1) and a mylin on glucose homeostasis in vivo in newborn dogs, euglycemic hyper -IGF-1 clamps and hypoglycemic hyper-IGF-l clamps were performed in ne wborn dogs. Northern blotting and radioimmunoassays were used to study the effects of the infused IGF-1 and/or hypoglycemia on the mRNA expr ession 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 greater than or equal to 1000 ng /ml) rapidly lowered the plasma glucose level, and 120 +/- 38 mg gluco se/pup was co-infused during a 105-min clamp to maintain the plasma gl ucose at the basal level. (2) The infused IGF-1 rapidly reduced the Li ver 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 pan creas, 106.7 +/- 14.2% vs 100.0 +/- 5.9% (controls), or on plasma amyl in 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 stim ulation by hypoglycemia in the presence of hyper-IGF-l. We concluded t hat (1) IGF-1 acutely suppressed cytosolic PEPCK gene expression in li ver of newborn dogs. (2) IGF-1 does not effect the expression of the p ancreatic amylin gene. (3) Amylin may be involved in glucose homeostas is in newborn dogs and may play a role as a counterregulatory factor d uring the neonatal period. Unsuppressed amylin production may contribu te to neonatal hyperglycemia. (C) 1996 Academic Press, Inc.