Diabetic nephropathy is markedly enhanced in mice lacking the bradykinin B2
Authors Kakoki M, Takahashi N, Jennette JC, Smithies O
Submitted By Oliver Smithies on 3/10/2009
Status Published
Journal Proceedings of the National Academy of Sciences of the United States of America
Year 2004
Date Published 9/7/2004
Volume : Pages 101 : 13302 - 13305
PubMed Reference 15326315
Abstract Type I human diabetics and streptozotocin-induced diabetic mice with higher
genetically determined levels of angiotensin-converting enzyme have an increased
risk of developing nephropathy. However, previous experiments in mice and
computer simulations indicate that modest increases in angiotensin-converting
enzyme have minimal effects on blood pressure and angiotensin II levels,
although bradykinin decreases significantly, inferring that bradykinin is
critical for protecting the kidney in diabetics. Here, we confirm this inference
by demonstrating that Akita diabetic mice lacking the bradykinin B2 receptor
develop overt albuminuria, excreting the equivalent of >550 mg/day albumin in
humans, which contrasts with the microalbuminuria (equivalent to <150 mg/day)
seen in their simply diabetic littermates. The overt albuminuria is accompanied
by a marked increase in glomerular mesangial sclerosis. The importance of
bradykinin demonstrated here bears strongly on how current drugs reduce diabetic
nephropathy and suggests that B2 receptor-specific agonists merit consideration
in this context.

Investigators with authorship
Oliver SmithiesUniversity of North Carolina


Aceangiotensin converting enzyme