Insulin regulates insulin-like growth factor I mRNA in rat hepatocytes.
To evaluate the regulatory role of growth hormone (GH) and insulin on insulin-like growth factor I (IGF-I) mRNA levels, we employed primary rat hepatocytes. Cells were incubated for 16 h with 10 nM insulin, 10 nM GH, or a combination thereof, and IGF-I mRNA levels were analyzed by Northern blotting. Insulin results in 2.5-fold and GH in 3.8-fold higher IGF-I mRNA levels than hormone-free controls, and a combination of insulin and GH had an additive effect (6.7-fold). The effect of 10 nM insulin was constant at variable GH concentrations. Therefore, GH and insulin affect IGF-I mRNA levels independently of each other. The half-maximal effective dose of insulin was 4.7 X 10(-10) M, and, in kinetic experiments, insulin was effective within 2 h. These findings demonstrate that insulin modulates hepatic IGF-I production by a direct regulation of the transcript levels of IGF-I.
Böni-Schnetzler
M
M
Metabolic Unit, University Hospital, Zürich, Switzerland.
Schmid
C
C
Meier
P J
PJ
Froesch
E R
ER
D000818:Animals; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects; D013006:Growth Hormone / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000235:genetics* / Q000494:pharmacology; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008954:Models, Biological; D009693:Nucleic Acid Hybridization; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification; D051381:Rats; D011919:Rats, Inbred Strains
D007328:Insulin; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone