Stephanie Kullmann1,2,3, Dominik Blum4, Benjamin Assad Jaghutriz1,2,3, Christoph Gassenmaier5, Benjamin Bender6, Hans-Ulrich Häring1,2,3, Gerald Reischl7, Hubert Preissl1,2,3,8,9, Christian la Fougère4,10, Andreas Fritsche1,2,3, Matthias Reimold4,10, Martin Heni1,2,3,11. 1. Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Germany. 2. German Center for Diabetes Research (DZD), Tübingen, Germany. 3. Department of Internal Medicine, Division of Endocrinology, Diabetology and Nephrology, Eberhard Karls University Tübingen, Tübingen, Germany. 4. Department of Nuclear Medicine and Clinical Molecular Imaging, Eberhard-Karls-University Tübingen, Tübingen, Germany. 5. Department of Internal Medicine, Division of Hematology, Oncology, Clinical Immunology and Rheumatology, Eberhard Karls University Tübingen, Tübingen, Germany. 6. Department of Diagnostic and Interventional Neuroradiology, University Hospital Tübingen, Tübingen, Germany. 7. Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tübingen, Tübingen, Germany. 8. Institute for Diabetes and Obesity, Helmholtz Diabetes Center at Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Neuherberg, Germany. 9. Department of Pharmacy and Biochemistry, Institute of Pharmaceutical Sciences, Eberhard Karls University Tübingen, Tübingen, Germany. 10. Cluster of Excellence iFIT (EXC 2180) "Image Guided and Functionally Instructed Tumor Therapies", University of Tübingen, Germany. 11. Institute for Clinical Chemistry and Pathobiochemistry, Department for Diagnostic Laboratory Medicine, University Hospital Tübingen, Tübingen, Germany.
Abstract
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.
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.
Authors: Jordi P D Kleinloog; Ronald P Mensink; Ellen T H C Smeets; Dimo Ivanov; Peter J Joris Journal: Neuroimage Clin Date: 2022-07-14 Impact factor: 4.891
Authors: Lore Wagner; Ralf Veit; Louise Fritsche; Hans-Ulrich Häring; Andreas Fritsche; Andreas L Birkenfeld; Martin Heni; Hubert Preissl; Stephanie Kullmann Journal: Int J Obes (Lond) Date: 2022-06-17 Impact factor: 5.551