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Diabetic nephropathy is markedly enhanced in mice lacking the bradykinin B2 receptor.


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.

SUBMITTER: Kakoki M 

PROVIDER: S-EPMC516527 | biostudies-literature | 2004 Sep

REPOSITORIES: biostudies-literature

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Diabetic nephropathy is markedly enhanced in mice lacking the bradykinin B2 receptor.

Kakoki Masao M   Takahashi Nobuyuki N   Jennette J Charles JC   Smithies Oliver O  

Proceedings of the National Academy of Sciences of the United States of America 20040823 36


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 diabet  ...[more]

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