1798-P: Insulin Modulates Dopaminergic Tone in the Human Brain—A Combined PET/MRI Study

Abstract

Insulin and dopamine signaling in the human brain are known modulators of whole-body glucose metabolism. Brain insulin resistance contributes to impaired postprandial glycemia and could predispose to type 2 diabetes. Experimental evidence suggests a crucial interaction between insulin and dopamine with dopaminergic dysfunction in brain insulin resistance. We now investigated the presence of such an interaction in the human brain. In 10 healthy young men (age 27±3 years, BMI 23.6±2.3 kg/m², HOMA-IR 1.8±1.1), we performed combined PET/MRI measurements using dynamic [11C]-Raclopride in combination with the intranasal application of 160 U insulin and placebo on two separate days in randomized, blinded order. Dopamine receptor binding potential as a measure of dopaminergic tone was estimated in regions of interests (ROI). Intranasal insulin delivery to the human brain increased dopamine receptor binding potential in the bilateral ventral and dorsal striatum, a major dopaminergic brain region (pFWE<0.001 cluster level). This response tended to be stronger in participants with higher BMI but was not statistically associated with HbA1c, fasting glucose, or HOMA-IR. Hence, insulin delivery to the human brain influences dopaminergic tone in the striatum. As earlier studies found insulin sensitivity of this region to be involved in the postprandial modulation of whole-body insulin sensitivity, the detected mechanism might be involved in the regulation of postprandial glycaemia. Alterations in this mechanism could therefore predispose to type 2 diabetes, a hypothesis that must be tested in further studies. Disclosure S. Kullmann: None. D. Blum: None. B. Jaghutriz: None. B. Bender: None. H. Haering: None. C. la Fougère: None. H. Preissl: None. A. Fritsche: None. M. Reimold: None. M. Heni: Research Support; Self; Boehringer Ingelheim International GmbH, Sanofi. Speaker's Bureau; Self; Lilly Diabetes, Merck Sharp & Dohme Corp., Sanofi. Funding German Federal Ministry of Education and Research