Glucose and other insulin secretagogues induce, rather than inhibit, expression of Id-1 and Id-3 in pancreatic islet beta cells

Aims/hypothesis. Basic helix loop helix transcription factors regulate insu lin gene transcription. Therefore, molecules that regulate their function s hould affect insulin production and secretion. As Id proteins inhibit basic helix loop helix function, it is important to determine whether they are e xpressed in beta cells and if insulin secretagogues regulate their expressi on. Methods. Human islets or insulinoma cells were cultured in different glucos e concentrations or treated with secretagogues. Insulin secretion was measu red using RIA. The Id mRNA and protein concentrations were measured using n orthern blots, RT-PCR, and western blots. Transfections of promoter-reporte r constructs were used to estimate Id-1 gene transcription. Results. The Id-1 mRNA concentrations were twofold higher in islets culture d overnight in 10 mmol/l than in 2.5 mmol/l glucose. Addition of high gluco se to islets previously cultured in low glucose, increased Id-1 mRNA concen trations within 30 min. Analyses using insulinoma cells revealed that Id-1 and Id-3 mRNA concentrations peaked 30 min after glucose was added, returne d to near basal concentrations by 2 h and then progressively increased for 24 h. The Id-1 protein concentrations changed in a similar pattern. Insulin secretagogues that act through different signaling pathways also induced I d expression. The Id response required glucose metabolism, calcium, and RNA synthesis but not protein synthesis. Glucose-responsive elements are confi ned to the 5'-region of the Id-1 gene. Conclusion/interpretation. The concomitant induction of Id-1 and Id-3 expre ssion, insulin gene transcription, and insulin secretion suggests that phys iological concentrations of Ids do not inhibit insulin gene transcription a nd Ids could play unexpected and novel roles in promoting beta-cell functio n.