Supplementary data for article: Central insulin modulates dopamine signaling in the human striatum

Objective: Activity in the dopaminergic pathways of the brain is highly
sensitive to body weight and metabolic states. Animal studies show that
dopamine neurons are important targets for the metabolic hormone insulin
with abolished effects in the insulin resistant state, leading to
increases in body weight and food intake. In humans, the influence of
central acting insulin on dopamine and effects of their interplay are
still elusive. Research Design and Methods: We investigated whether
central administered insulin influences dopaminergic activity in striatal
regions and whole-brain neural activity. Using a PET/MRI hybrid scanner,
we simultaneously performed [11C]-raclopride-PET and resting state fMRI in
10 healthy normal weight men after application of intranasal insulin or
placebo on two separate days in a randomized, placebo-controlled, blinded,
crossover trial. Results: In response to central insulin compared to
placebo administration, we observed greater [11C]-raclopride binding
potential (BPnd) in the bilateral ventral and dorsal striatum. This
suggests an insulin-induced reduction in synaptic dopamine levels.
Resting-state striatal activity was lower 15 and 30 min after nasal
insulin compared to placebo. Functional connectivity of the
mesocorticolimbic circuitry associated with differences in dopamine
levels: individuals with a stronger insulin-induced effect on dopamine
levels showed a stronger increase in functional connectivity 45 min after
intranasal insulin.­ Conclusions: This study indicates that central
insulin modulates dopaminergic tone in the striatum, which may affect
regional brain activity and connectivity. Our results deepen the
understanding of the insulin-dopamine interaction and the complex network
that underlies the regulation of whole-body metabolism.