Essentiality of intron control in the induction of c-fos by glucose and glucoincretin peptides in INS-1 β-cells

Glucose controls long-term processes in the pancreatic β-cell such as metabolic enzymes gene expression, cell growth, and apoptosis. Such control is likely mediated via the expression of immediate-early response genes since several of these genes including c-fos are strongly induced by glucose in the β-cell line INS-1, provided costimulation with cAMP-raising glucoincretin hormones. This study addresses the mechanism of c-fos gene activation by glucose. Glucose in the presence of chlorophenylthio-cAMP generated a low threefold induction of the c-fos/basic luciferase reporter gene, which includes only the c-fos promoter. In contrast, the c-fos/intron construct containing the first intron in addition to promoter elements showed a pronounced 16-fold induction, comparable to the increased c-fos mRNA accumulation. Similar observations were made with glucose in combination with the glucoincretins glucagon-like peptide 1, glucose-dependent insulinotropic polypeptide, and pituitary adenylyl cyclase-activating pep...