Central Insulin Modulates Dopamine Signaling in the Human Striatum.
Stephanie Kullmann, Dominik Blum, Benjamin Assad Jaghutriz, Christoph Gassenmaier, Benjamin Bender, Hans-Ulrich Häring, Gerald Reischl, Hubert Preissl, Christian la Fougère, Andreas Fritsche, Matthias Reimold, Martin Heni
Author Information
Stephanie Kullmann: Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Germany. ORCID
Dominik Blum: Department of Nuclear Medicine and Clinical Molecular Imaging, Eberhard-Karls-University Tübingen, Tübingen, Germany.
Benjamin Assad Jaghutriz: Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Germany.
Christoph Gassenmaier: Department of Internal Medicine, Division of Hematology, Oncology, Clinical Immunology and Rheumatology, Eberhard Karls University Tübingen, Tübingen, Germany.
Benjamin Bender: Department of Diagnostic and Interventional Neuroradiology, University Hospital Tübingen, Tübingen, Germany.
Hans-Ulrich Häring: Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Germany.
Gerald Reischl: Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tübingen, Tübingen, Germany.
Hubert Preissl: Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Germany. ORCID
Christian la Fougère: Department of Nuclear Medicine and Clinical Molecular Imaging, Eberhard-Karls-University Tübingen, Tübingen, Germany.
Andreas Fritsche: Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Germany.
Matthias Reimold: Department of Nuclear Medicine and Clinical Molecular Imaging, Eberhard-Karls-University Tübingen, Tübingen, Germany.
Martin Heni: Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Germany. ORCID
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 positron emission tomography (PET)/magnetic resonance imaging (MRI) hybrid scanner, we simultaneously performed [11C]-raclopride-PET and resting-state functional MRI in 10 healthy normal-weight men after application of intranasal insulin or placebo on 2 separate days in a randomized, placebo-controlled, blinded, crossover trial. RESULTS: In response to central insulin compared with placebo administration, we observed greater [11C]-raclopride binding potential 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 minutes after nasal insulin compared with 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 minutes 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.
