Mechanism Found That May Protect Kidneys

[Guest guest]

>

>

> 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 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), which dilates blood

> vessels and helps eliminate excess water and sodium from the kidneys. ACE

> inhibitors do not block ACE2 production.

>

> " Since AngII over-production is thought to play a pivotal role in the

> progression of diabetic nephropathy, we suggest that decreased renal ACE

activity

> coupled with increased renal ACE2 expression may be protective for the

> kidneys in the early phases of diabetes by limiting the renal accumulation of

AngII

> and possibly by favoring Ang(1-7) formation, as well, " Batlle said.

>

> Interestingly, the finding of a decrease in ACE activity and an increase in

> ACE2 expression in the young mouse model, is similar to a pattern seen after

> administering a kidney-protecting drug and ACE inhibitor called ramipril to

> diabetic rats, Batlle said.

>

> Batlle said that an increased ACE2 level in the kidneys in early diabetes

> does not exclude the possibility of an ACE2 reduction later, during the course

> of the disease as kidney damage develops. He believes it is possible that

> with time decreased ACE2 expression with an increase in ACE may foster damage

> in diabetes.

>

> " The significance of a reduction in ACE coupled with increased ACE2

> production in the " kidneys needs to be further studied but there is every

reason to

> believe that it can only be beneficial, " Batlle said.

>

> " We know that giving ACE inhibitors can protect against kidney disease, but

> we need to learn more about ACE2 in diabetes, obesity and hypertension, " he

> said.

>

> Kidney disease is among the most common complications of diabetes,

> affecting over 20 percent of the 17 million diabetic patients in the United

States.

>

> In addition to Ye, Batlle's co-researchers on the study were Jan Wysocki,

> Parveen Naaz, Mohammad Reza Salabat and S. LaPointe of the Feinberg

> School.

>

>

>

> Source: Northwestern University

>

>

>

>

>

>

>