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Hummel, J. ; Benkendorff, C.* ; Fritsche, L. ; Prystupa, K.* ; Vosseler, A.* ; Gancheva, S.* ; Trenkamp, S.* ; Birkenfeld, A.L. ; Preissl, H. ; Roden, M.* ; Häring, H.-U. ; Fritsche, A. ; Peter, A. ; Wagner, R.* ; Kullmann, S. ; Heni, M.

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

Nat. Metab. 5, 1475-1482 (2023)

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Insulin action in the human brain modulates eating behaviour, whole-body metabolism and body fat distribution1,2. In particular, brain insulin action increases whole-body insulin sensitivity, but these studies were mainly performed in lean men3,4. 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 spray5–7 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.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Endogenous Glucose-production; Intranasal Insulin; Differential Sensitivity; Sex-hormones; Resistance; Humans; Metabolism; Overweight; Hyperinsulinemia; Hypothalamus

ISSN (print) / ISBN 2522-5812

e-ISSN 2522-5812

Journal Nature metabolism

Quellenangaben Volume: 5, Issue: 9, Pages: 1475-1482

Publisher Springer

Publishing Place London

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Diabetes Research and Metabolic Diseases (IDM)

Grants German Federal Ministry of Education and Research (BMBF)