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.

The insulin resistant brain: impact on whole-body metabolism and body fat distribution

“…This condition is most commonly associated with overweight and obesity [ 25 ]. Additionally, further factors are also linked to brain insulin resistance, including normal ageing [ 41 , 49 , 50 ], circulating levels of NEFA [ 35 ] and different common genetic polymorphisms [ 36 – 38 , 51 , 52 ], most of which were discovered due to their association with body weight. Though, the direct role of these factors in causing brain insulin resistance is still under research.…”

Peripheral insulin resistance attenuates cerebral glucose metabolism and impairs working memory in healthy adults

“…Much of this research has studied people with conditions in which insulin resistance is a hallmark characteristic, including ageing, type 2 diabetes and Alzheimer's disease (see (6)(7)(8) for a reviews). This research suggests that peripheral and central insulin resistance are linked (9,10) and that clinical levels of insulin resistance are an important contributor to age-related diseases and cognitive decline (11)(12)(13). Moreover, the risk of cognitive decline often starts in midlife and increases as the duration and severity of insulin resistance increases (14).…”

“…Much of this research has focussed on conditions in which insulin resistance is a hallmark characteristic, such as type 2 diabetes, Alzheimer’s disease and ageing (see (6-8) for a reviews). This research suggests that peripheral and central insulin resistance are linked (9, 10) and that insulin resistance is an important contributor to age-related diseases and cognitive decline (11-13).…”