Glucose-stimulated insulin biosynthesis depends on insulin-stimulated insulin gene transcription

Glucose stimulation of pancreatic p-cells leads to insulin secretion as wel l as up-regulation of insulin biosynthesis. The acute elevation in pro-insu lin levels is thought to be exclusively because of the activation of transl ation of pre existing prepro-insulin mRNA. Glucose-stimulated insulin gene transcription is believed to be a long term effect and should therefore not contribute to the acute elevation in pro-insulin levels. We have recently shown that glucose activates insulin gene transcription within minutes and that secreted insulin is one of the key factors triggering this process in an autocrine manner. We now provide evidence that 50% of the glucose-stimul ated, acute pro-insulin biosynthesis within 30 min results from up-regulate d insulin gene transcription. Our data led us to propose that glucose eleva tes pro-insulin levels by stimulating both transcriptional and post-transcr iptional/post-translational events to an equal extent. Whereas the stimulat ory effect on transcription is mediated by insulin secreted in response to glucose, glucose directly stimulates the post-transcriptional/post-translat ional processes.