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Using the brain to fight diabetes: How overeating impairs insulin

Kathleen Blanchard's picture
Researchers discover how overeating impairs insulin in the brain.

Obesity is a known risk factor for type 2 diabetes, but how it develops is poorly understood. Now researchers have discovered that overeating impairs insulin function in the brain to prevent breakdown of fat tissue. The result of a high calorie diet, according to the new findings, is that fatty acids are released into the bloodstream; causing inflammation and insulin resistance.

Brain insulin controls glucose release

Christoph Buettner, MD, PhD, Associate Professor of Medicine (Endocrinology, Diabetes and Bone Disease) at The Mount Sinai Hospital/Mount Sinai School of Medicine and his team previously found that brain insulin stops the release of fatty acids in the bloodstream. The research was published in 2011 in the journal Cell Metabolism. Fatty acids are the by-product of triglycerides.

Researchers also know that fatty acids produce inflammation which is a hallmark of type 2 diabetes.

Buettner explains in a press release, "We are interested in understanding why people who eat too much eventually develop diabetes. Our recent studies suggest that once you overeat, your brain develops insulin resistance. Since brain insulin controls lipolysis [fat breakdown] in adipose [fat] tissue by reducing sympathetic nervous system outflow to adipose tissue, brain insulin resistance causes increased spillage of fatty acids from adipose tissue into the blood stream," said Dr. Buettner.

How the study was done

Researchers fed rats a high fat diet consisting of 10% lard for 5 days in a row, which boosted their daily calories by 50%. They used another group of rats as a control that was given a low-fat diet.

Next they injected a small amount of insulin into the rat’s brains. The researchers already knew from previous studies the insulin would slow glucose release in the liver and suppress fatty acid release from fat tissue.

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The found that a high fat diet impairs the brain’s ability to slow down glucose release. The same thing happens in humans just from over-eating for a short period of time, perhaps from the same mechanism

Dr. Buettner said, “When you overeat, your brain becomes unresponsive to these important clues such as insulin, which puts you on the road to diabetes. We believe that what happens in rats also happens in humans.”

A study published November, 2011 also supports the notion that the brain controls glucose levels in the body. Current thinking is that the pancreas is responsible for insulin release.

The study, titled "Activation of KATP channels suppresses glucose production in humans" was published in the Journal of Clinical Investigation.

Researchers used a drug on humans called diazoxide to activate potassium channels in the brain, which in turn signals the liver to produce less glucose.

Buettner's team plans to explore ways to boost brain insulin function that could curb insulin resistance, obesity and type 2 diabetes. Another approach being explored is targeting the brain with drugs that suppress glucose release in the liver.

"The Journal of Biological Chemistry"
"Short Term Voluntary Overfeeding Disrupts Brain Insulin Control of Adipose Tissue Lipolysis"
Thomas Scherer, et al.
October, 2012

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