Dataset Information

Brain insulin action on peripheral insulin sensitivity in women depends on menstrual cycle phase.

ABSTRACT: Insulin action in the human brain modulates eating behaviour, whole-body metabolism and body fat distribution^1,2. In particular, brain insulin action increases whole-body insulin sensitivity, but these studies were mainly performed in lean men^3,4. Here we investigate metabolic and hypothalamic effects of brain insulin action in women with a focus on the impact of menstrual cycle ( ClinicalTrials.gov registration: NCT03929419 ).Eleven women underwent four hyperinsulinemic-euglycemic clamps, two in the follicular phase and two in the luteal phase. Brain insulin action was introduced using nasal insulin spray^5-7 and compared to placebo spray in a fourfold crossover design with change in glucose infusion rate as the primary endpoint. Here we show that during the follicular phase, more glucose has to be infused after administration of nasal insulin than after administration of placebo. This remains significant after adjustment for blood glucose and insulin. During the luteal phase, no significant influence of brain insulin action on glucose infusion rate is detected after adjustment for blood glucose and insulin (secondary endpoint). In 15 other women, hypothalamic insulin sensitivity was assessed in a within-subject design by functional magnetic resonance imaging with intranasal insulin administration⁸. Hypothalamus responsivity is influenced by insulin in the follicular phase but not the luteal phase.Our study therefore highlights that brain insulin action improves peripheral insulin sensitivity also in women but only during the follicular phase. Thus, brain insulin resistance could contribute to whole-body insulin resistance in the luteal phase of the menstrual cycle.

SUBMITTER: Hummel J

PROVIDER: S-EPMC10513929 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

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Brain insulin action on peripheral insulin sensitivity in women depends on menstrual cycle phase.

Hummel Julia J Benkendorff Charlotte C Fritsche Louise L Prystupa Katsiaryna K Vosseler Andreas A Gancheva Sofiya S Trenkamp Sandra S Birkenfeld Andreas L AL Preissl Hubert H Roden Michael M Häring Hans-Ulrich HU Fritsche Andreas A Peter Andreas A Wagner Robert R Kullmann Stephanie S Heni Martin M

Nature metabolism 20230921 9

Insulin action in the human brain modulates eating behaviour, whole-body metabolism and body fat distribution<sup>1,2</sup>. In particular, brain insulin action increases whole-body insulin sensitivity, but these studies were mainly performed in lean men<sup>3,4</sup>. Here we investigate metabolic and hypothalamic effects of brain insulin action in women with a focus on the impact of menstrual cycle ( ClinicalTrials.gov registration: NCT03929419 ).Eleven women underwent four hyperinsulinemic-eu ...[more]

PMID: 37735274

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Project description:Dopamine (DA) plays a major role in reinforcement learning with increases promoting reward sensitivity (Go learning) while decreases facilitate the avoidance of negative outcomes (NoGo learning). This is also reflected in adaptations of response time: higher levels of DA enhance speeding up to get a reward, whereas lower levels favor slowing down. The steroid hormones estradiol and progesterone have been shown to modulate dopaminergic tone. Here, we tested 14 women twice during their menstrual cycle, during the follicular (FP) and the luteal phase (LP), applying functional magnetic resonance imaging while they performed a feedback learning task. Subsequent behavioral testing assessed response time preferences with a clock task, in which subjects had to explore the optimal response time (RT) to maximize reward. In the FP subjects displayed a greater learning-related change of their RT than during the LP, when they were required to slow down. Final RTs in the slow condition were also predicted by feedback-related brain activation, but only in the FP. Increased activation of the inferior frontal junction and rostral cingulate zone was thereby predictive of slower and thus better adapted final RTs. Conversely, final RT was faster and less optimal for reward maximization if activation in the ventromedial prefrontal cortex was enhanced. These findings show that hormonal shifts across the menstrual cycle affect adaptation of response speed during reward acquisition with higher RT adjustment in the FP in the condition that requires slowing down. Since high estradiol levels during the FP increase synaptic DA levels, this conforms well to our hypothesis that estradiol supports Go learning at the expense of NoGo learning. Brain-behavior correlations further indicated that the compensatory capacity to counteract the follicular Go bias may be linked to the ability to more effectively monitor action outcomes and suppress bottom-up reward desiring during feedback processing.

Dataset Information

Brain insulin action on peripheral insulin sensitivity in women depends on menstrual cycle phase.

Publications

Brain insulin action on peripheral insulin sensitivity in women depends on menstrual cycle phase.

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