Local formation of angiotensin peptides with paracrine activity by adipocytes

A local paracrine angiotensin (ANG) system influences the insulin sensitivity and cell differentiation of adipose tissue. The limited view of a merely systemic renin-angiotensin-aldosterone-system with ANG II (1-8) as the main mediator of ANG-related effects may oversimplify the situation. The aim was to analyze the degradation of ANG by using capillary electrophoresis (CE) techniques. The supernatant of cultured 3T3-L1 adipocytes was used directly, and some data on degraded peptides were combined with a biological effect. The formation of several peptides such as ANG II (1-8), -III (2-8), -IV (3-8), and ANG (1-7) as degradation products is demonstrated; in addition low levels of ANG (3-7) are identified. The concentrations of the peptides ANG III (2-8) and ANG IV (3-8) (both are AT(4) receptor agonists) are modified in the vicinity of adipose tissue cells by amino-terminal degradation which resulted in ANG (3-8), -(4-8) and -(5-8). ANG IV (3-8) and ANG II (1-8) were biologically highly effective in inhibiting IRAP (insulin regulated aminopeptidase, part of the AT(4) receptor). It is observed that ANG (1-7) is the main degradation product derived from ANG I via ANG (1-9) and that ANG III (2-8) is one important regulated peptide for IRAP.