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Diabetes may clamp down on cholesterol the brain needs
Date:11/30/2010

memory loss and eating disorders than people without diabetes, and imaging studies have shown that people with diabetes have altered brain function compared to those without.

Additionally, the finding raises a question about potential interactions between anti-cholesterol drugs and diabetes.

In the Joslin study, scientists first examined gene expression in the hypothalamus of a mouse model of insulin-deficient (type 1) diabetes. They found decreased expression for almost all of the genes of cholesterol synthesis, including a gene called SREBP-2, which acts as a master regulator for cholesterol production. Similar findings were present in the cerebral cortex and other regions of the brain in these animals and also found in several other mouse models of diabetes. In the insulin-deficient animals, this phenomenon was associated with decreased cholesterol synthesis. Treatment of the mice with insulin, either by normal injection or injection into the fluid surrounding the brain, reversed the process.

"Our studies showed that these effects occurred in both the neurons and supporting 'glial' cells that help provide some nutrients to the neurons," says Kahn. "Ultimately this affects the amount of cholesterol that can get into the membranes of the neuron, which form the synapses and the synaptic vesiclesthe small structures that contain neurotransmitters."

Additionally, the Joslin work showed a connection between the decrease in brain cholesterol synthesis and appetite. When the scientists took normal mice and temporarily reduced cholesterol creation in the hypothalamus with a technique known as RNA interference, the animals started eating more and gained significant weight. Previous studies by other labs have demonstrated that diabetes may affect brain hormones involved in appetite regulation.


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Contact: Eric Bender
eric.bender@joslin.harvard.edu
617-309-2418
Joslin Diabetes Center
Source:Eurekalert

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