Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Stressing Glucose: At the Crossroads of Early Life Adversity, HPA Axis Reactivity and Carbohydrate Metabolism

Snehaa Vivienne Seal
ORCID logo ,
Myriam Merz
ORCID logo ,
Sara Beatriz Fernandes
,
Sophie B. Meriaux
,
Pauline Guebels
,
Jamileh Movassat
,
Muriel Darnaudery
ORCID logo ,
Martha M. C. Elwenspoek
,
Fleur A. D. Leenen
,
Claude P. Muller
,
Hartmut Schächinger
,
Jonathan D. Turner
* ORCID logo
Version 1 : Received: 20 July 2022 / Approved: 21 July 2022 / Online: 21 July 2022 (07:53:13 CEST)

How to cite: Seal, S.V.; Merz, M.; Fernandes, S.B.; Meriaux, S.B.; Guebels, P.; Movassat, J.; Darnaudery, M.; Elwenspoek, M.M.C.; Leenen, F.A.D.; Muller, C.P.; Schächinger, H.; Turner, J.D. Stressing Glucose: At the Crossroads of Early Life Adversity, HPA Axis Reactivity and Carbohydrate Metabolism. Preprints 2022, 2022070311. https://doi.org/10.20944/preprints202207.0311.v1 Seal, S.V.; Merz, M.; Fernandes, S.B.; Meriaux, S.B.; Guebels, P.; Movassat, J.; Darnaudery, M.; Elwenspoek, M.M.C.; Leenen, F.A.D.; Muller, C.P.; Schächinger, H.; Turner, J.D. Stressing Glucose: At the Crossroads of Early Life Adversity, HPA Axis Reactivity and Carbohydrate Metabolism. Preprints 2022, 2022070311. https://doi.org/10.20944/preprints202207.0311.v1

Abstract

External stressors strongly increase cardiovascular activity and induce metabolic changes that ensure the availability of glucose and oxygen as part of a co-ordinated stress response. Exposure to stress during early life appears to have an exaggerated long-term effect on this response, leading to an increased risk or cardiometabolic disorders. Here we demonstrate that acute stress induced glucose release is impacted by the early life environment in rodent maternal deprivation and early-life infection models and this was validated in our EpiPath human early-life adversity cohort. In all three models differences in baseline blood glucose levels after ELA exposure were sex dependent. The human ELA model showed higher levels of basal glucose in females, similar to the mouse infection and rat maternal deprivation models. We anticipated that the stress induced glucose rise would be a GC dependent process. However, the kinetics of stress-induced glucose release, peaking 15-28 minutes before cortisol suggest that it is a GC-independent process. We confirmed this by administering an escalating dose of cortisol to a health human cohort, and the inability of an intravenous GC bolus induce a glucose rise in man confirms that it is a rapid, GC independent, process.In conclusion, we provide a novel perspective on the mechanisms behind stress related metabolic changes and highlights the importance of collecting early life data as a measure to understand an individual’s metabolic status in a better light.

Keywords

glucose; cortisol; corticosterone; stress; early life adversity

Subject

Biology and Life Sciences, Endocrinology and Metabolism

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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