Differential effects of intranasal insulin and caffeine on cerebral blood flow

Insulin is an important modulator of brain functions such as memory and appetite regulation. Besides the effect on neuronal activity, it is also possible that insulin has a direct vasodilatory effect on cerebral blood flow (CBF). We investigated the impact of increased insulin levels in the central nervous system on basal and task-induced CBF as well as blood oxygenation level-dependent (BOLD) response in the visual cortex using pulsed arterial spin-labeling MRI. An intranasal insulin application was used to avoid peripheral hyperinsulinaemia, which would lead to a cascade of hormonal changes. In a control experiment, caffeine was applied due to its well-known impact on the vasculature of the brain leading to a reliable reduction of CBF. Eight lean subjects were included in the study. On 2 separate days, intranasal human insulin or caffeine tablets were given to the subjects after fasting over night. On each day, basal CBF and task-induced CBF were measured before and 30 min after application of insulin or caffeine in each subject. During the task condition, a flickering checkerboard was presented. Insulin had no effect on basal CBF and task-induced CBF in comparison with drug-free baseline measurement in the visual cortex and control regions. After caffeine application, however, there was a significant decrease of CBF during stimulation in the visual cortex. The BOLD response was not altered by insulin or caffeine between pre- and postdose measurements. In conclusion, we found no evidence for a direct vasodilatory effect of intranasal insulin on the cerebral vascular system in this study.