Researchers find direct link between insulin resistance and behavioral disorders

March 2, 2015, Joslin Diabetes Center
insulin
High-resolution model of six insulin molecules assembled in a hexamer. Credit: Isaac Yonemoto/Wikipedia

People with diabetes are more prone to anxiety and depression than those with other chronic diseases that require similar levels of management. The reasons for this aren't well understood, but Joslin Diabetes Center researchers have discovered one potential explanation.

Genetically modifying mice to make their brains resistant to insulin, the Joslin scientists first found that the animals exhibited behaviors that suggest , and then pinpointed a mechanism that lowers levels of the key in areas of the brain associated with those conditions.

"This is one of the first studies that directly shows that insulin resistance in the brain actually can produce a behavioral change," says C. Ronald Kahn, MD, who is Joslin's Chief Academic Officer and the Mary K. Iacocca Professor of Medicine at Harvard Medical School, and senior author on a paper reporting the work in the journal PNAS.

His research team assessed the genetically modified mice in multiple tests that place mice under stress and are commonly used to analyze drugs that treat anxiety and depression. Young mice behaved much like normal mice, but mice tested at 17 months of age ("which is starting late middle-age for mice," notes Dr. Kahn) displayed significant behavioral disorders.

Examining the brains of these mice, the scientists found altered metabolism in mitochondria, which produce energy for cells. Among the changes, the mitochondria increased production of two enzymes that degrade dopamine, a major transmitter of brain behavior. "These mice release a normal amount of dopamine, but because of these changes in the mitochondria they metabolize that dopamine faster, and it's not around as long," explains Dr. Kahn. "We think that contributes to these behaviors, and in fact when we give the mice antidepressants that work by slowing dopamine degradation, we can correct some of the behavioral changes."

Although the behavioral effects were not seen in the younger genetically modified mice, the scientists detected similar changes in their brain cells as well. It's not clear why the changes in behavior might increase with age, Kahn says, but the effect is common among mouse models of neurological disorders, and is seen in the same human neurological diseases.

Previous research in both mice and humans has made connections between insulin resistance and other neurodegenerative conditions, especially Alzheimer's disease. Clinical studies have shown that patients with Alzheimer's demonstrate reduced levels of certain insulin signaling proteins, suggesting a role for insulin resistance in those diseases, Dr. Kahn says. Additionally, previous research by his lab demonstrated in that alters a protein known as tau in a way that is a marker of early abnormalities in Alzheimer's.

"Preliminary studies have shown that treating people with Alzheimer's disease with insulin inhaled through the nose, which is supposed to allow more insulin to get delivered directly to the brain, might slow their changes in cognitive function," he adds. "It's obviously too early to tell, because we're looking at very early-stage research, but one could imagine that intranasal insulin might actually have some effects in anti-depression or anti-anxiety in people with diabetes."

Explore further: Tale of 2 mice pinpoints major factor for insulin resistance

More information: Insulin resistance in brain alters dopamine turnover and causes behavioral disorders, PNAS, www.pnas.org/cgi/doi/10.1073/pnas.1500877112

Related Stories

Tale of 2 mice pinpoints major factor for insulin resistance

May 16, 2011
The road to type 2 diabetes is paved with insulin resistance, a condition often associated with obesity in which the hormone begins to fail at its job helping to convert sugars to energy. Researchers at Joslin Diabetes Center ...

Unexpected turn in diabetes research

January 20, 2015
Years of diabetes research carried out on mice whose DNA had been altered with a human growth hormone gene is now ripe for reinterpretation after a new study by researchers at KU Leuven confirms that the gene had an unintended ...

Inducing insulin resistance: Human iPS cell model offers new look at key driver of type 2 diabetes

August 1, 2014
(Medical Xpress)—Harvard Medical School researchers at Joslin Diabetes Center have created the first induced pluripotent stem cells (iPSCs) that offer a human model of insulin resistance, a key driver of type 2 diabetes.

Molecular link between obesity and type 2 diabetes reveals potential therapy

February 23, 2015
Obesity causes inflammation, which can in turn lead to type 2 diabetes. What isn't well established is how inflammation causes diabetes—or what we can do to stop it. Researchers at University of California, San Diego School ...

Maternal insulin resistance changes pancreas, increases metabolic disorders risk in offspring

December 2, 2014
A growing proportion of women of childbearing age are among the estimated one in three Americans who have insulin resistance—a metabolic disorder that can be a precursor to a number of health problems, including diabetes, ...

Recommended for you

LincRNAs identified in human fat tissue

June 21, 2018
A large team of researchers from the U.S. and China has succeeded in identifying a number of RNA fragments found in human fat tissue. In their paper published in the journal Science Translational Medicine the group describes ...

Scientists solve the case of the missing subplate, with wide implications for brain science

June 21, 2018
The disappearance of an entire brain region should be cause for concern. Yet, for decades scientists have calmly maintained that one brain area, the subplate, simply vanishes during the course of human development. Recently, ...

Key molecule of aging discovered

June 21, 2018
Every cell and every organism ages sooner or later. But why is this so? Scientists at the German Cancer Research Center in Heidelberg have now discovered for the first time a protein that represents a central switching point ...

Compound made inside human body stops viruses from replicating

June 20, 2018
The newest antiviral drugs could take advantage of a compound made not by humans, but inside them. A team of researchers has identified the mode of action of viperin, a naturally occurring enzyme in humans and other mammals ...

Research reveals zero proof probiotics can ease your anxiety

June 20, 2018
If you're expecting probiotics to reduce your anxiety, it might be time to put down that yogurt spoon—or supplement bottle—and call a professional instead.

Long-term estrogen therapy changes microbial activity in the gut, study finds

June 20, 2018
Long-term therapy with estrogen and bazedoxifene alters the microbial composition and activity in the gut, affecting how estrogen is metabolized, a new study in mice found.

1 comment

Adjust slider to filter visible comments by rank

Display comments: newest first

gettingwell
1 / 5 (1) Mar 09, 2015
The unexplainable causes in this study included why genetically insulin-resistant mice developed symptoms of anxiety and depressive-like behaviors between early adulthood and late middle age.

Humans most often develop insulin-resistance symptoms for causes other than genetics, such as a result of abnormal eating behaviors, which are themselves symptoms of other causes.

Use of the insulin-resistant-due-to-genetics mice may have misdirected the researchers to lose focus that their ultimate task was to find ways that their research can help humans.

If helping humans was the researchers' focus, it may have occurred to them to contribute to the research that proves how "something" caused a symptom such as abnormal eating behaviors, that in turn caused a symptom of insulin resistance.

http://surfaceyou...ealself/

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.