Researchers at Academic Medical Center (AMC) found that dopamine signaling is a key regulator of systemic glucose metabolism, which could guide exploration of new targets or interventions to increase insulin sensitivity in patients with chronic diseases such as Type II diabetes. The findings appeared in Science Translational Medicine.
Research has pointed toward a potential relationship between striatal dopamine activity and glucose regulation. In this study, the AMC group found direct evidence of this interplay in humans and mice, beginning with a case study in a diabetic patient whose total daily insulin dose decreased after he underwent deep brain stimulation as a striatal dopamine-releasing therapy to treat his severe obsessive-compulsive disorder (OCD).
In the 55-year-old OCD patient with insulin-dependent Type II diabetes, deep brain stimulation decreased insulin use, suppressed endogenous glucose production (EGP) and free fatty acids at higher rates, and increased glucose rate of disappearance compared with no stimulation, suggesting improved liver, adipose tissue and muscle insulin sensitivity.
Striatal dopamine release via deep brain stimulation also led to increased EGP suppression and glucose rate of disappearance in 14 non-diabetic OCD patients, with greater peripheral insulin sensitivity in the seven lean patients.
Conversely, the researchers found that a tyrosine hydroxylase (TYH) inhibitor known to induce acute systemic dopamine depletion decreased insulin sensitivity in 10 healthy lean men.
In mice, optogenetic stimulation of dopamine D1 receptor-positive neurons in the same striatal region stimulated by deep brain stimulation reduced plasma glucose compared with no stimulation, suggesting activating the neurons increased glucose tolerance. Plasma insulin concentrations were comparable under both conditions, suggesting increased insulin sensitivity -- as opposed to increased insulin secretion -- led to greater glucose tolerance.
Study author Mireille Serlie told BioCentury the team plans to identify major pathways involved in how deep brain stimulation and dopamine affect glucose metabolism.
Serlie added that future research should investigate whether deep brain stimulation or other brain devices or drugs can stimulate or inhibit certain pathways in the brain to enhance glucose regulation to treat diabetes. Serlie said deep brain stimulation is "pretty invasive," but the therapy has low complication rates and can be reversed.