Glucose induces insulin gene transcription in a murine pancreatic beta-cell line.

Abstract

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.