Researchers from the German Center for Diabetes Research in Tübingen reported that an interaction between insulin and dopamine in the striatum region of the brain can alter the regulation of glucose metabolism and eating behaviors. The scientists determined that obesity leading to changes in brain's signaling can adversely impact glucose metabolism in the entire body. Their results were published in November 2021 in the Journal of Clinical Endocrinology & Metabolism.

Lead author Stephanie Kullmann, Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Germany, German Center for Diabetes Research, Tübingen; Eberhard Karls, University of Tübingen; and colleagues investigated the effect of exogenously administered insulin on dopamine activity in both the whole and specific striatal region of the brain. This research was based on the current understanding of these dopamine pathways and their highly sensitive responses to metabolic state and weight. Previous animal studies demonstrated that lower dopamine activity in the presence of insulin resistance leads to increased caloric intake and body weight.

"Our eating behavior is regulated by the interaction between the reward system and homeostatic systems. Studies indicate that insulin also acts in dopamine-driven reward centers in the brain. It has also been shown that obesity leads to changes in the signaling of the brain that have a negative effect on the glucose metabolism in the whole body," said Dr. Kullmann. "We now wanted to decipher the interaction between the two systems in humans and find out how insulin regulates the dopamine system," she added.

In a study conducted on 2 separate days in a randomized, placebo-controlled, blinded, crossover trial, the team evaluated a cohort of 10 healthy, normal-weight men who received insulin or a placebo via a nasal spray. When insulin is absorbed via the nose, it reaches the brain directly. To study the interaction between insulin and dopamine, the researchers used a unique measurement technique: They combined resting-state functional MRI to assess functional brain activity and positron emission tomography to assess dopamine levels. Then, they reported the response, which for those who received insulin were observed to have greater binding potential of [11C]-raclopride, the dopamine D2/3 receptor ligand widely used for assessment of synaptic levels of dopamine, in both the dorsal and bilateral ventral striatum. This is suggestive of insulin-induced decreases of synaptic dopamine levels.

"The study provides direct evidence of how and where in the brain signals triggered after eating—such as insulin release and the reward system—interact," said Professor Martin Heni, last author of the study, summarizing the results. He added, "We were able to show that insulin is able to decrease dopamine levels in the striatum in normal-weight individuals. The insulin-dependent change in dopamine levels was also associated with functional connectivity changes in whole-brain networks. Changes in this system may be an important driver of obesity and related diseases."

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