Brain insulin responsiveness is linked to age and peripheral insulin sensitivity

Abstract Aims Insulin action in the brain influences cognitive processes, peripheral metabolism and eating behaviour. However, the influence of age and peripheral insulin sensitivity on brain insulin action remains unclear. Materials and Methods We used intranasal administration of insulin and functional magnetic resonance imaging in a randomized, placebo‐controlled within‐subject design in 110 participants (54 women, body mass index 18‐49 kg/m 2 , age 21‐74 years). Cerebral blood flow was measured before and after nasal spray application to assess brain insulin action. Peripheral insulin sensitivity was assessed by a five‐point oral glucose tolerance test. Linear regressions were used to investigate associations between age and peripheral insulin sensitivity with brain insulin action in predefined region of interests (i.e. insulin‐sensitive brain regions). Results We found significant negative associations between age and insulin action in the hippocampus (β = –0.215; p = .017) and caudate nucleus (β = –0.184; p = .047); and between peripheral insulin sensitivity and insulin action in the amygdala (β = –0.190, p = .023). Insulin action in the insular cortex showed an interaction effect between age and peripheral insulin sensitivity (β = –0.219 p = .005). Furthermore, women showed the strongest negative association between age and hippocampal insulin action, while men showed the strongest associations with peripheral insulin sensitivity and age in reward‐related brain regions. Conclusion We could show a region‐specific relationship between brain insulin responsiveness, age and peripheral insulin sensitivity. Our findings underline the need to study brain insulin action in both men and women and further substantiate that brain insulin sensitivity is a possible link between systemic metabolism and neurocognitive functions.