Insulin resistance in the brain can actually cause behavioural changes in diabetics, a new study has found.
People with diabetes are more prone to anxiety and depression than those with other chronic diseases that require similar levels of management, researchers said.
Scientists genetically modified mice to make their brains resistant to insulin.
They found the animals exhibited behaviours that suggest anxiety and depression, and then pinpointed a mechanism that lowers levels of the key neurotransmitter dopamine 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 behavioural change,” said C Ronald Kahn, Joslin Diabetes Centre’s Chief Academic Officer and Professor of Medicine at Harvard Medical School.
The research team assessed the genetically modified mice in multiple tests that place mice under stress and are commonly used to analyse 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,” noted Kahn) displayed significant behavioural 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 behaviour.
“These mice release a normal amount of dopamine, but because of these changes in the mitochondria they metabolise that dopamine faster, and it’s not around as long,” said Kahn.
“We think that contributes to these behaviours, and in fact when we give the mice antidepressants that work by slowing dopamine degradation, we can correct some of the behavioural changes,” said Kahn, senior author on a paper published in the journal PNAS.
Although the behavioural effects were not seen in the younger genetically modified mice, the scientists detected similar changes in their brain cells as well.
It is not clear why the changes in behaviour might increase with age, Kahn said, 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.