Insulin resistance and the transcription of the glucose-6-phosphatase gene in newborn dogs.
In the present report changes in the mRNA level of glucose-6-phosphatase (G6Pase; EC 3.1.39) in newborn and adult dogs in vivo were studied to further test the hypotheses that neonatal hyperglycemia may be due to unsuppressed gluconeogenesis by insulin and that the antidiabetic role of insulin-like growth factor-1 (IGF-1) may be intact in newborn dogs who have consistently demonstrated insulin resistance. Our results were the following: (i) Both renal and hepatic G6Pase mRNA were expressed at birth and increased with time during a 24-h period of fasting after birth. (ii) The renal G6Pase mRNA levels in newborn dogs did not respond to either insulin or epinephrine. (iii) Hyperinsulinemia lowered the liver G6Pase mRNA by only 16.3% in newborn dogs, but reduced the liver G6Pase mRNA to an undetectable level in adult dogs. (iv) Hyperglycemia decreased the hepatic G6Pase mRNA by 14.3% in newborn dogs under hyperinsulinemia. (v) Infused epinephrine did not elevate the hepatic G6Pase mRNA level in newborn dogs in the presence of hyperglycemia and hyperinsulinemia. (vi) In newborn dogs, hyper-IGF-1 rapidly reduced the hepatic G6Pase mRNA level by 50%, and hypoglycemia was unable to elevate the hepatic G6Pase mRNA level under the hyper-IGF-1. We concluded that the reduced rate of suppression of transcription of the liver G6Pase gene by insulin in newborn dogs may reflect the unsuppressed neonatal hepatic gluconeogenesis due to insulin resistance and that the physiological roles of IGF-1 seemed to be intact in newborn dogs and may be not responsible for neonatal hyperglycemia.
Feng
B C
BC
Department of Pediatrics, Medical College of Wisconsin, Milwaukee 53226, USA.
Li
J
J
Kliegman
R M
RM
D000818:Animals; D000831:Animals, Newborn; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D004285:Dogs; D004837:Epinephrine / Q000494:pharmacology; D005786:Gene Expression Regulation; D005943:Gluconeogenesis; D005952:Glucose-6-Phosphatase / Q000235:genetics*; D006943:Hyperglycemia / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D007328:Insulin / Q000097:blood / Q000494:pharmacology; D007333:Insulin Resistance / Q000235:genetics*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
D007328:Insulin; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D005952:Glucose-6-Phosphatase; D004837:Epinephrine