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Orexins control intestinal glucose transport by distinct neuronal, endocrine, and direct epithelial pathways

Robert Ducroc1, Thierry Voisin, Aadil El Firar

  • 1Institut National de la Santé et de la Recherche Médicale U773, Centre de Recherche Biomédicale Bichat-Beaujon, 16 rue Henri Huchard, BP16, 75870 Paris cedex 18, France. ducroc@bichat.inserm.fr

Diabetes
|July 14, 2007
PubMed
Abstract

Insights

Orexin A (OxA) and orexin B (OxB) inhibit intestinal glucose absorption in rats, decreasing blood glucose levels. This suggests a new role for orexins in regulating energy homeostasis.

Area of Science:

  • Neuroendocrinology
  • Gastroenterology
  • Metabolic Regulation

Background:

  • Orexins are neuropeptides crucial for energy homeostasis.
  • Intestinal glucose absorption plays a key role in regulating blood glucose levels and overall energy balance.

Purpose of the Study:

  • To investigate the effects of orexin A (OxA) and orexin B (OxB) on intestinal glucose transport in rats.
  • To elucidate the mechanisms underlying orexin-mediated regulation of glucose absorption.

Main Methods:

  • Oral glucose tolerance tests (OGTTs) were performed in rats following orexin administration.
  • Jejunal glucose transport was quantified in Ussing chambers by measuring the Na(+)-dependent increase in short-circuit current (Isc).
  • The involvement of neuronal and endocrine pathways was assessed using tetrodotoxin (TTX), cholecystokinin (CCK) 2R antagonists, and OX(1)R antagonist SB334867.

Main Results:

  • Both OxA and OxB significantly decreased blood glucose levels during OGTTs.
  • OxA and OxB inhibited glucose-induced Isc in the jejunum, indicating reduced glucose transport.
  • OxA's inhibitory effect involved neuronal and CCK-releasing cells via OX(2)R, while OxB acted directly on enterocytic OX(1)R.

Conclusions:

  • Orexins function as inhibitors of intestinal glucose absorption.
  • These findings establish a novel role for orexins in the short-term control of energy homeostasis.
  • Distinct orexin receptor pathways mediate the differential effects of OxA and OxB on glucose transport.

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