Imaging the brain to assess brain insulin action

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AbstractBackgroundEver since the brain was identified as an insulin‐sensitive organ, it was quickly appreciated that insulin action in the brain affects cognitive and metabolic processes [1]. Epidemiological evidence suggests a strong link between reduced peripheral insulin sensitivity and age‐related neurodegenerative processes, including Alzheimer’s disease (AD) [2].MethodCharacterization of brain insulin resistance in humans is challenging and relies on different neuroimaging methods in combination with insulin stimulation techniques. In my talk, I will focus on the administration of intranasal insulin, which has been established over the last decades to disentangle peripheral from brain insulin effects [1]. In combination with functional neuroimaging, I will show recent data on the quantification of brain insulin sensitivity non‐invasively in humans of different age and weight groups [3].ResultWe could show that intranasal insulin can affect region‐specific activity and functional connectivity of the human brain. These diverse central insulin responses largely depend on its action in the hypothalamus, amygdala, hippocampus, striatum and parts of the insula and prefrontal cortex and influences a variety of metabolic and cognitive processes [3]. Specifically, I will show that disrupted brain insulin action can result in increased accumulation of visceral fat and altered reward learning in persons at high risk to develop T2D [4], but also in healthy individuals after overconsumption of high caloric foods (unpublished). Moreover, I will show that the effect of intranasal insulin in the hippocampus decreases with age in women but not men and that brain insulin responsivity is affected by the menstrual cycle (unpublished). Moreover, just recently, we could link enhanced brain insulin action in the mesocorticolimbic circuitry with improved cognitive and metabolic functions [5].ConclusionAs brain insulin acts on striatal dopamine function and hippocampal plasticity, enhancing brain insulin action could lead to new treatment options in diabetes and aging‐associated diseases.