Characterization of a putative insulin-responsive element and its binding protein(s) in rat angiotensinogen gene promoter: regulation by glucose and insulin.

We previously demonstrated that high glucose activates angiotensinogen (ANG) expression and that insulin inhibits this activation. The present studies aim to investigate whether insulin regulates ANG gene expression in kidney proximal tubular cells at the transcription level via interaction of the putative insulin-response element (IRE) with its binding protein(s) in the 5′-flanking region of the ANG gene. Fusion genes containing various lengths of the 5′-flanking region of the rat ANG gene fused to a human GH (hGH) gene as reporter were constructed and transiently introduced into rat immortalized renal proximal tubular cells (IRPTCs). The expression of the fusion genes was monitored by the amount of immunoreactive hGH secreted into the medium as assayed by a specific RIA for hGH. Insulin inhibited the expression of pOGH (rANG N-1498/+18), pOGH (rANG N-1120/+18) and pOGH (rANG N-882/+18) but not pOGH (rANG N-854/+18), pOGH (rANG N-820/+18), pOGH (rANG N-688/+18) and pOGH (rANG N-53/+18) in high-glucose (i...