Effect of insulin action on central dopamine signaling in normal-weight and obese participants (PET-MR)

Cerebral insulin resistance plays an important role in the development of obesity and diabetes mellitus type 2. The aim of this project is to examine the effect of human nasal insulin on the dopaminergic system. Therefore, characteristics of cerebral dopamine receptors before and after administration of nasal insulin vs. placebo are analyzed in a randomized way. Moreover, insulin action on cortical and subcortical activation in humans and the interaction of dopamine metabolism with [11C]-Raclopride-PET/MRI is investigated. By performing fMRI measurements, insulin sensitivity of the central nervous system can be investigated simultaneously. 10 normal-weight (BMI 20-25 kg/m²) and 10 overweight/obese men will be examined.

  

With the study we pursue two main objectives

  • Effect of nasal insulin vs. placebo on the insulin sensitivity of the human brain as well as on regional availability of dopamine receptors.
  • Differences between normal weight and obese participants regarding insulin sensitivity and availability of dopamine receptors assessed by fMRI and Raclopride-PET/MRT.

 

Project supervisor

Prof. Dr. Andreas Fritsche

Study registration

NCT03637075

Project-related publications

Central nervous pathways of insulin action in the control of metabolism and food intake.

Kullmann S, Kleinridders A, Small DM, Fritsche A, Häring HU, Preissl H, Heni M. Lancet Diabetes Endocrinol. 2020 Jun;8(6):524-534. doi: 10.1016/S2213-8587(20)30113-3.

Dose-Dependent Effects of Intranasal Insulin on Resting-State Brain Activity.

Kullmann S, Veit R, Peter A, Pohmann R, Scheffler K, Häring HU, Fritsche A, Preissl H, Heni M. J Clin Endocrinol Metab. 2018 Jan 1;103(1):253-262. doi: 10.1210/jc.2017-01976.

Hypothalamic and Striatal Insulin Action Suppresses Endogenous Glucose Production and May Stimulate Glucose Uptake During Hyperinsulinemia in Lean but Not in Overweight Men.

Heni M, Wagner R, Kullmann S, Gancheva S, Roden M, Peter A, Stefan N, Preissl H, Häring HU, Fritsche A. Diabetes. 2017 Jul;66(7):1797-1806. doi: 10.2337/db16-1380.

Interaction between the obesity-risk gene FTO and the dopamine D2 receptor gene ANKK1/TaqIA on insulin sensitivity.

Heni M, Kullmann S, Ahlqvist E, Wagner R, Machicao F, Staiger H, Häring HU, Almgren P, Groop LC, Small DM, Fritsche A, Preissl H. Diabetologia. 2016 Dec;59(12):2622-2631. doi: 10.1007/s00125-016-4095-0.