Identification of a novel rat hepatic gene induced early by insulin, independently of glucose.
We used mRNA differential display to identify new genes induced early after exposure to insulin. Our screening strategy was based on the comparison of gene expression during the time course of insulin induction in the liver of 12-day-old suckling rats both in vivo and in vitro. A novel, early induced transcript, EIIH, was identified that encodes a 353-amino-acid protein with several features suggesting that it may be secreted or bound to membranes. EIIH is also distantly related to a variety of LRR (leucine-rich repeat) proteins. Insulin treatment increased EIIH mRNA levels in the hepatocytes of suckling, fasted adult and STZ (streptozotocin)-treated diabetic rats, where insulin was required to maintain the basal level of EIIH expression. EIIH expression was induced during the suckling/weaning transition, and remained detectable thereafter. Tissue distribution analysis in adult rats revealed a pattern of expression mainly in the liver, intestine and islets of Langerhans, closely following that of the Glut2 (glucose transporter 2), suggesting that it may play a role in carbohydrate metabolism. EIIH may be a primary target of the transcriptional regulation by insulin, and may therefore constitute a new model to study the mechanisms by which insulin acts on gene transcription.
Coffy
Sandrine
S
Institut Cochin, INSERM U567, CNRS UMR8104, Département d'Endocrinologie, Université Paris 5, 24 rue du Faubourg Saint-Jacques, 75014 Paris, France.
Decaux
Jean-François
JF
Girard
Jean
J
de Keyzer
Yves
Y
Asfari
Maryam
M
D000375:Aging / Q000235:genetics; D000818:Animals; D000833:Animals, Suckling; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000235:genetics; D004958:Estradiol / Q000494:pharmacology; D005215:Fasting; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D005941:Glucokinase / Q000235:genetics; D005947:Glucose / Q000494:pharmacology; D051273:Glucose Transporter Type 2; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology*; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000196:embryology / Q000378:metabolism*; D008297:Male; D008969:Molecular Sequence Data; D009004:Monosaccharide Transport Proteins / Q000235:genetics; D011506:Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats
D051273:Glucose Transporter Type 2; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D011506:Proteins; D012333:RNA, Messenger; C501294:Tsku protein, rat; D004958:Estradiol; D005941:Glucokinase; D005947:Glucose