Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany.
German Center for Diabetes Research (DZD e.V.), Tübingen, Germany.
Diabetes Obes Metab. 2023 Aug;25(8):2171-2180. doi: 10.1111/dom.15094. Epub 2023 May 4.
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.
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 , 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).
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.
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.
大脑中的胰岛素作用会影响认知过程、外周代谢和进食行为。然而，年龄和外周胰岛素敏感性对大脑胰岛素作用的影响仍不清楚。
我们采用随机、安慰剂对照的自身对照设计，在 110 名参与者（54 名女性，体重指数 18-49kg/m²，年龄 21-74 岁）中使用鼻内胰岛素给药和功能磁共振成像。在鼻腔喷雾应用前后测量脑血流，以评估大脑胰岛素作用。通过五点口服葡萄糖耐量试验评估外周胰岛素敏感性。使用线性回归分析来研究年龄和外周胰岛素敏感性与大脑胰岛素作用之间的关系，研究对象为预先设定的感兴趣区域（即胰岛素敏感的脑区）。
我们发现，年龄与海马体（β=-0.215，p=0.017）和尾状核（β=-0.184，p=0.047）中的胰岛素作用呈显著负相关；外周胰岛素敏感性与杏仁核（β=-0.190，p=0.023）中的胰岛素作用呈负相关。岛叶皮质中的胰岛素作用表现出年龄和外周胰岛素敏感性之间的交互效应（β=-0.219，p=0.005）。此外，女性的年龄与海马体胰岛素作用之间的负相关性最强，而男性则表现出与奖励相关脑区的外周胰岛素敏感性和年龄之间的最强相关性。
我们能够证明大脑胰岛素反应性、年龄和外周胰岛素敏感性之间存在特定区域的关系。我们的研究结果强调了在男性和女性中研究大脑胰岛素作用的必要性，并进一步证实大脑胰岛素敏感性是全身代谢和神经认知功能之间的一个可能联系。
