Glucose induces insulin gene transcription in a murine pancreatic beta-cell line.
The ability of insulin secretagogues to stimulate insulin gene transcription was analyzed in the murine insulinoma cell line beta TC3, which had been derived from a transgenic mouse expressing SV40 T antigen under control of the rat insulin II gene regulatory region. Glucose induced a 3-fold increase in the transcription of both the endogenous mouse insulin genes and the transgene. This effect was inhibited by D600, a calcium channel blocker, which also inhibited glucose-induced insulin secretion in these cells. This suggests that similar signals may be involved in glucose-stimulated insulin secretion and insulin gene transcription. Agents that increase intracellular levels of cAMP did not have a significant effect on the transcription of either the insulin genes or the transgene. Stimulation of transcription of the RIP-Tag transgene by glucose suggests that the 695-base pair fragment of the insulin gene regulatory region that is included in the transgene contains the cis elements required for response to the glucose-induced signal.
Efrat
S
S
Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York 10461.
Surana
M
M
Fleischer
N
N
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology; D005711:Gallopamil / Q000494:pharmacology; D005796:Genes / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology*; D007328:Insulin / Q000235:genetics*; D007340:Insulinoma; D007700:Kinetics; D051379:Mice; D008822:Mice, Transgenic; D010190:Pancreatic Neoplasms; D011401:Promoter Regions, Genetic; D051381:Rats; D014158:Transcription, Genetic / Q000187:drug effects*; D014544:Uridine Triphosphate / Q000378:metabolism
D007328:Insulin; D005576:Colforsin; D005711:Gallopamil; D000242:Cyclic AMP; D005947:Glucose; D015056:1-Methyl-3-isobutylxanthine; D014544:Uridine Triphosphate