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Glycogen Supercompensation in the Rat Brain After Acute Hypoglycemia is Independent of Glucose Levels During Recovery

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Abstract

Patients with diabetes display a progressive decay in the physiological counter-regulatory response to hypoglycemia, resulting in hypoglycemia unawareness. The mechanism through which the brain adapts to hypoglycemia may involve brain glycogen. We tested the hypothesis that brain glycogen supercompensation following hypoglycemia depends on blood glucose levels during recovery. Conscious rats were submitted to hypoglycemia of 2 mmol/L for 90 min and allowed to recover at different glycemia, controlled by means of i.v. glucose infusion. Brain glycogen concentration was elevated above control levels after 24 h of recovery in the cortex, hippocampus and striatum. This glycogen supercompensation was independent of blood glucose levels in the post-hypoglycemia period. In the absence of a preceding hypoglycemia insult, brain glycogen concentrations were unaltered after 24 h under hyperglycemia. In the hypothalamus, which controls peripheral glucose homeostasis, glycogen levels were unaltered. Overall, we conclude that post-hypoglycemia glycogen supercompensation occurs in several brain areas and its magnitude is independent of plasma glucose levels. By supporting brain metabolism during recurrent hypoglycemia periods, glycogen may have a role in the development of hypoglycemia unawareness.

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Acknowledgements

This work was supported by the Swiss National Science Foundation (SNSF, Grant 122498), the National Institutes of Health (Grant R01NS042005), and the Centre d’Imagerie BioMédicale (CIBM) of the UNIL, UNIGE, HUG, CHUV, EPFL and the Leenaards and Jeantet Foundations. JMND was supported by the SNSF Ambizione program (Grant 148250). The authors are grateful to Dr. Igor Allaman (Laboratory of Neuroenergetics and Cellular Dynamics, EPFL) and Dr. Ana F. Soares (LIFMET, EPFL) for fruitful discussions.

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Authors and Affiliations

  1. Laboratory for Functional and Metabolic Imaging (LIFMET), Ecole Polytechnique Fédérale de Lausanne (EPFL), Station 6, 1015, Lausanne, Switzerland

    João M. N. Duarte & Rolf Gruetter

  2. Cellular Imaging Facility, University of Lausanne, Lausanne, Switzerland

    Florence D. Morgenthaler

  3. Department of Radiology, University of Lausanne, Lausanne, Switzerland

    Rolf Gruetter

  4. Department of Radiology, University of Geneva, Geneva, Switzerland

    Rolf Gruetter

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  1. João M. N. Duarte
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  2. Florence D. Morgenthaler
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  3. Rolf Gruetter
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Correspondence to João M. N. Duarte.

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Duarte, J.M.N., Morgenthaler, F.D. & Gruetter, R. Glycogen Supercompensation in the Rat Brain After Acute Hypoglycemia is Independent of Glucose Levels During Recovery. Neurochem Res 42, 1629–1635 (2017). https://doi.org/10.1007/s11064-017-2178-z

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  • DOI: https://doi.org/10.1007/s11064-017-2178-z

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