Insulin-like growth factor-II gene expression in a rat insulin-producing beta-cell line (INS-1) is regulated by glucose.
A highly differentiated rat glucose-responsive insulin producing cell line INS-1 expresses high levels of insulin-like growth factor-II (IGF-II). Basal levels of IGF-II gene mRNA were expressed in cells cultured at 1-6 mmol/l glucose. At glucose concentrations of 10-20 mmol/l, IGF-II mRNA was increased more than threefold after 44 h of incubation. Levels of IGF-II mRNA in INS-1 cells incubated at 5.6 and 20 mmol/l glucose in the presence of 4 micrograms/ml actinomycin D are comparable and are not reduced during 20 h of treatment, indicating the high stability of IGF-II mRNA in this cell line. From the three rat IGF-II promoters, promoter 3 is by far the most active in INS-1 cells. The IGF-II promoter 3 activity and IGF-II mRNA production at high glucose concentrations increased threefold over their respective levels at low glucose concentration, suggesting that the glucose-induced IGF-II gene expression in this beta-cell line might be transcriptionally controlled. The up-regulation of IGF-II mRNA by glucose was not due to the increased intracellular cyclic AMP levels or protein kinase C activation. A protein kinase C activator had no effect on IGF-II gene expression, and an adenylate cyclase activator (forskolin), suppressed the stimulatory effects of glucose on the IGF-II mRNA. Under all the experimental conditions examined, the IGF-II and insulin genes were differentially regulated in INS-1 cells. The IGF-II gene expression and DNA synthesis, however, were regulated in parallel, suggesting that these two cellular activities are closely associated.
Asfari
M
M
INSERM CJF-9313, Hôpital Robert Debré, Paris, France.
De
W
W
Nöel
M
M
Holthuizen
P E
PE
Czernichow
P
P
D000818:Animals; D002460:Cell Line; D005576:Colforsin / Q000494:pharmacology; D004247:DNA / Q000096:biosynthesis; D015342:DNA Probes; D003609:Dactinomycin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects*; D005947:Glucose / Q000494:pharmacology*; D007328:Insulin / Q000096:biosynthesis*; D007335:Insulin-Like Growth Factor II / Q000096:biosynthesis*; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D008156:Luciferases / Q000096:biosynthesis; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D051381:Rats; D011994:Recombinant Proteins / Q000096:biosynthesis; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism; D014162:Transfection
D015342:DNA Probes; D007328:Insulin; D012333:RNA, Messenger; D011994:Recombinant Proteins; D003609:Dactinomycin; D005576:Colforsin; D007335:Insulin-Like Growth Factor II; D004247:DNA; D008156:Luciferases; D005947:Glucose; D013755:Tetradecanoylphorbol Acetate; D013936:Thymidine