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Lack of insulin damages kidneys: high blood sugar is not only cause for concern in diabetics.

Diabetic kidney disease may result as much from a failure of certain renal cells to access insulin as it does from runaway blood sugar, a new study shows. The finding suggests that targeting the condition known as insulin resistance might protect the kidneys of people with diabetes, researchers report in the October Cell Metabolism.

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Half of all kidney disease that leads to dialysis or a transplant occurs in diabetics, most often people with the type 2 form that typically shows up in adulthood. Type 2 diabetes has clear links to obesity, lack of exercise and insulin resistance, in which cells fail to capture glucose efficiently from the bloodstream after digestion of food. While the precise cause of insulin resistance remains unclear, there's no question it starves cells, forces the pancreas to work overtime making more insulin and leaves a person with high blood sugar.

In the new study, researchers examined cells called podocytes that form part of the blood-cleansing apparatus of the kidneys. The researchers suspected that insulin resistance might damage these filtration cells and therefore underlie the kidney damage common to people with diabetes.

To test that hypothesis, the team genetically engineered mice with podocytes that lacked insulin-receptor proteins. In these mice, podocytes were largely unable to bind to the insulin needed to orchestrate the use of glucose in the cells. Within several weeks the animals showed podocyte damage, allowing leakage of crucial blood proteins called albumins into the urine. Such albumin loss is a telltale sign of kidney problems, says team member Richard Coward of the University of Bristol in England.

This damage showed up, he says, even though the mice didn't have high blood sugar, suggesting that insulin resistance plays a role in kidney disease brought on by diabetes, called diabetic nephropathy.

"This paper turns some of the thinking about diabetic nephropathy on its head," says Sian Griffin, a nephrologist at the University Hospital of Wales in Cardiff. "Previous treatment has focused on optimizing glycemic control, but these experiments suggest a potential novel therapeutic paradigm--that diabetic nephropathy might be prevented or even reversed by targeting the podocyte insulin-signaling pathway in itself."

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Title Annotation:Body & Brain
Author:Seppa, Nathan
Publication:Science News
Geographic Code:1USA
Date:Nov 6, 2010
Words:356
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