Insulin levels affect the brain's dopamine systems
Insulin, long known as an important regulator of blood glucose levels, now has a newly appreciated role in the brain.
Vanderbilt University Medical Center researchers, working with colleagues in Texas, have found that insulin levels affect the brain's dopamine systems, which are involved in drug addiction and many neuropsychiatric conditions.
In addition to suggesting potential new targets for treating drug abuse, the findings raise questions as to whether improper control of insulin levels - as in diabetes - may impact risk for attention deficit hyperactivity disorder (ADHD) or influence the effectiveness of current ADHD medications.
Working with Galli and Avison, Jason Williams, Ph.D., used fMRI to demonstrate that in normal, healthy rats with plenty of insulin, amphetamine increased neural activity in the striatum. But in diabetic animals, activity in the striatum was suppressed.
"This finding is in vivo evidence that, in the intact diabetic rat, loss of insulin has compromised DAT trafficking to the plasma membrane," Avison said. "These experiments show that there is likely a strong interplay between these important dopamine neurotransmitter systems and insulin signaling mechanisms, which we know are altered in diabetes"
The results are some of the first to link insulin status and dopaminergic brain function and hold several implications for human health and disease.
"This is really the first mechanistic connection in vivo between diabetes and amphetamine action," Galli said. "This offers a completely new perspective on the influence of this disease (diabetes) on brain function, as well as diseases with altered dopamine signaling, such as schizophrenia and ADHD."