[Diabetes-talk] insulin gards against artery damage

[Debbie Fredericks]

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Discovery Diary: Joslin shows insulin guards against artery damage
From: Joslin Diabetes Center <editor at joslin.harvard.edu>View Contact 
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Joslin shows insulin guards against artery damage
  
Christian Rask-Madsen, M.D., Ph.D., lead author on Cell Metabolism paper 
Long suspected of worsening artery damage in patients with diabetes, insulin instead protects blood vessels, a new study by scientists here at Joslin Diabetes Center indicates. 
  
This important discovery came from Joslin basic research efforts. If you would like to provide financial support to basic research at Joslin, click here to give online.


 
For decades, medical researchers have debated whether insulin can promote atherosclerosis, the buildup of cholesterol in blood vessels that causes coronary artery disease and stroke. This was a particular concern for those patients with type 2 diabetes who need insulin injections to control their blood glucose levels. 
My laboratory in the Dianne Nunnally Hoppes Laboratory for Diabetes Complications now has produced clear evidence that insulin protects arteries. Our work was published on May 5 in Cell Metabolism online.
Extrapolating the findings to humans would suggest that physicians should not be so wary of prescribing insulin to patients with diabetes. It also raises the exciting possibility of designing special insulins that interact directly with blood vessels, potentially slowing atherosclerosis in these patients.
Our study focused on endothelial cells, the cells lining the inside of blood vessels in which atherosclerotic plaques develop. 
We began with a line of mice in which the gene for the insulin receptor has been knocked out in endothelial cells only. In these mice, endothelial cells are unresponsive to insulin. 
“Mice don’t get atherosclerosis unless their normal cholesterol metabolism is changed,” notes Christian Rask-Madsen, M.D., Ph.D., a research associate in our lab and lead author on the paper. So the insulin-receptor knockout mice were crossed with another line of mice, known as ApoE mice, which has elevated cholesterol levels in the blood.  Dr. Rask-Madsen and his colleagues then compared how atherosclerosis developed in these mice compared to standard ApoE mice.
The two groups of mice showed similar levels of other factors known to promote cardiovascular disease, including blood pressure, glucose metabolism and the levels of lipids in the blood. 
But we found that the insulin-receptor knockout mice were on a fast track to atherosclerosis.  The insulin-receptor knockout mice developed cholesterol plaques that were more than twice the size of those found in the control animals. 
Taken altogether, the evidence “suggests that if you can improve insulin action in endothelial cells, you may be able to slow or prevent atherosclerosis,” notes Dr. Rask-Madsen. 

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