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Glucokinase and glucokinase regulatory proteins are functionally coexpressed before birth in the rat brain

I Roncero1, C Sanz, E Alvarez

  • 1Department of Biochemistry and Molecular Biology, Faculty of Medicine, Complutense University, Madrid, Spain. ironcero@med.ucm.es

Journal of Neuroendocrinology
|October 8, 2009
PubMed

Insights

Functional glucokinase (GK) and glucokinase regulatory protein (GKRP) are present and active in fetal rat brains, suggesting a role in early glucose sensing and food intake control before birth.

Area of Science:

  • Neuroscience
  • Metabolism
  • Developmental Biology

Background:

  • Glucokinase (GK) and glucokinase regulatory protein (GKRP) are implicated in central nervous system glucose sensing in adults.
  • Their presence and activity in the developing brain remain largely uncharacterized.

Purpose of the Study:

  • To investigate the coexpression and functional activity of GK and GKRP in fetal and early postnatal rat brains.
  • To determine if these proteins are active before birth and contribute to early glucose sensing mechanisms.

Main Methods:

  • Analysis of GK and GKRP mRNA and protein expression in fetal and pup rat brains.
  • Immunohistochemistry to assess protein colocalization.
  • Coprecipitation assays to detect protein interactions.
  • Enzymatic assays to measure GK phosphorylating activity in brain extracts.

Main Results:

  • GK and GKRP mRNAs and proteins were detected in fetal rat brains, mirroring adult expression patterns.
  • Immunohistochemistry confirmed colocalization of GK and GKRP proteins within the same brain cells of 21-day-old fetuses.
  • Coprecipitation demonstrated interaction between GK and GKRP in the presence of fructose 6-phosphate.
  • Functional GK activity was found in various fetal brain regions, notably the hypothalamus, contributing significantly to glucose phosphorylation.

Conclusions:

  • Both GK and GKRP are expressed and potentially interact in the fetal rat brain before birth.
  • These proteins appear functionally active, suggesting a role in a fetal glucose sensor system.
  • This system may be involved in the early control of food intake during development.

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