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Fasting mediated increase in p-BAD(ser155) and p-AKT(ser473) in the prefrontal cortex of mice

Vigneshwaran Pitchaimani1, Somasundaram Arumugam1, Rajarajan Amirthalingam Thandavarayan2

  • 1Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata 956-8603, Japan.

Neuroscience Letters
|July 22, 2014
PubMed

Insights

Fasting impacts brain regions differently, affecting key proteins like p-BAD and p-AKT. This influences beta-hydroxybutyrate (BHB) uptake and hormonal responses during hypoglycemia, particularly in the prefrontal cortex.

Area of Science:

  • Neuroscience
  • Metabolic Regulation
  • Endocrinology

Background:

  • Fasting and BAD-deficiency share roles in seizures, beta-hydroxybutyrate (BHB) uptake, and counterregulatory hormonal regulation during hypoglycemia.
  • Neuronal specific insulin receptor knockout (NIRKO) mice exhibit impaired counterregulatory hormonal responses during hypoglycemia.

Purpose of the Study:

  • Investigate fasting-mediated expression of phosphorylated BAD (p-BAD at serine 155) and phosphorylated AKT (p-AKT at serine 473) in distinct brain regions.
  • Determine the role of these signaling pathways in regulating BHB uptake and hormonal responses during hypoglycemia.

Main Methods:

  • Utilized BAD-deficient mice and fasting models.
  • Analyzed expression levels of p-BAD(ser155) and p-AKT(ser473) in the prefrontal cortex, hippocampus, midbrain, and hypothalamus.
  • Examined counterregulatory hormonal responses during hypoglycemia.

Main Results:

  • Fasting specifically increased p-BAD(ser155) and p-AKT(ser473) in the prefrontal cortex.
  • Fasting decreased p-BAD(ser155) and p-AKT(ser473) in the hippocampus, midbrain, and hypothalamus.
  • Fasting-mediated hypoglycemia activated prefrontal cortex insulin signaling, influencing sympathoadrenal hormonal responses via the hypothalamic paraventricular nucleus.

Conclusions:

  • Fasting differentially regulates p-BAD and p-AKT expression across brain regions, impacting BHB uptake and hormonal responses during hypoglycemia.
  • The prefrontal cortex plays a specific role in mediating fasting-induced changes in insulin signaling and counterregulatory hormonal activation.
Keywords:
AKTBADBetahydroxybutyrateFastingHypoglycemiaPrefrontal cortex

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