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Effects of acute hypoglycemia on the orexin system in rat

Yu-yan Zhao1, Lei Guo, Jian Du

  • 1Department of Endocrinology, the First Affiliated Hospital, China Medical University, Shenyang 110001. g572@sina.com

Chinese Medical Sciences Journal = Chung-Kuo I Hsueh K'O Hsueh Tsa Chih
|April 23, 2005
PubMed
Abstract

Insights

Acute glucose changes impact orexin system. Hypoglycemia boosts orexin mRNA in the hypothalamus, while feeding inhibits it. Glucose also modulates prepro-orexin gene expression in pancreatic islets.

Area of Science:

  • Neuroscience
  • Endocrinology
  • Molecular Biology

Background:

  • The orexin system regulates feeding behavior and energy homeostasis.
  • Orexin neurons in the hypothalamus are sensitive to glucose levels.
  • The role of glucose in modulating orexin gene expression in pancreatic islets is not well understood.

Purpose of the Study:

  • To investigate the effects of acute glucose level fluctuations on the expression of prepro-orexin, orexin 1 receptor (OX1R), and orexin 2 receptor (OX2R) mRNA.
  • To examine these effects in both rat hypothalamus and pancreatic islet cells.

Main Methods:

  • Adult male Wistar rats were subjected to acute hypoglycemia induced by insulin injection.
  • Rats were either allowed to eat freely or were food-deprived post-hypoglycemia.
  • Gene expression of prepro-orexin and OXRs was analyzed using RT-PCR in hypothalamus and in vitro cultured pancreatic islet cells exposed to varying glucose concentrations (2.8 mmol/L and 8.3 mmol/L).

Main Results:

  • Food-deprived hypoglycemic rats showed a significant increase (150%) in hypothalamic orexin mRNA expression compared to controls (P < 0.01).
  • Hypothalamic OX1R mRNA expression decreased by 30% (P < 0.01), while OX2R mRNA remained unchanged.
  • In vitro, pancreatic islet cells exposed to low glucose (2.8 mmol/L) exhibited a twofold increase in prepro-orexin mRNA expression compared to high glucose (8.3 mmol/L) (P < 0.01).
  • OX1R mRNA expression in islets was insensitive to acute glucose fluctuations.

Conclusions:

  • Orexin gene expression in the rat hypothalamus is stimulated by decreased blood glucose and inhibited by feeding signals.
  • Glucose plays a significant role in modulating prepro-orexin gene expression within rat pancreatic islet cells.
  • These findings highlight the intricate interplay between glucose metabolism and the orexin system in energy regulation.

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