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Mechanism found that may protect kidneys in early stages of diabetes

A group of Northwestern University researchers has identified what they believe is a built-in biological mechanism that prevents kidney damage in the early stages of diabetes associated with obesity.

Their study was led by Daniel Batlle, M.D., Earle, del Greco, Levin Professor of Nephrology and professor of medicine at Northwestern University Feinberg School of Medicine, and was published in the May issue of the journal Hypertension.

Batlle and colleagues assessed the activity of two enzymes, ACE (for angiotensin-converting enzyme) and ACE2, which play an important role in the control of blood pressure, in the kidneys of a young mouse model of obesity and diabetes. The mouse, called db/db, develops type 2, insulin-resistant diabetes and obesity at around four to seven weeks after birth and eventually manifests some, but not all, features of human diabetic nephropathy.

In eight-week old db/db mice, which were obese and had high levels of blood glucose but no evidence of diabetes-related kidney disease, the researchers found low levels of a substance known as ACE (for angiotensin-converting enzyme) and increased levels of a related enzyme, ACE2.

The significance of a reduction in ACE coupled with increased ACE2 production in the kidneys needs to be clarified, said Minghao Ye, research associate in medicine at the Feinberg School and first author on the study.

ACE is required for production of angiotensin II (AngII), which, among its actions, causes blood vessel constriction and sodium and water retention by the kidney, leading to hypertension and kidney damage.

ACE inhibitors, which block production of AngII, are commonly used to treat high blood pressure and heart failure, as well as to improve survival after a heart attack and slow progression of kidney disease in individuals with diabetes.

ACE2, which was recently discovered, prevents accumulation of AngII while promoting formation of another substance called Ang(1-7), whi
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Contact: Elizabeth Crown
e-crown@northwestern.edu
312-503-8928
Northwestern University
13-May-2004


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