Background & aim: 

The orexogenic peptide orexin-A is expressed in endocrine cells in duodenal mucosa and stimulates duodenal alkaline secretion. However, stimulation occurs only in animals with continuous access to food; overnight fasting thus abolishes the response to orexin-A. Our aim was to identify luminal factors regulating this feeding-status dependency.

Methods: 

Different isocalometric nutrients (glucose, lactalbumin and corn oil) were given to overnight fasted Lewis x Dark Agouti rats by enteral feeding. Animals were then anesthetized and proximal duodenum cannulated in situ. Titration of duodenal alkaline secretion was started 4 hours after gavage and orexin-A was administered to the duodenum by close intra-arterial infusion. Total RNA was extracted from enterocytes isolated from continuously fed or overnight (16 hours) fasted animals and expression levels of orexin receptors (OX1R and OX2R) measured by quantitative real-time PCR.

Results: 

Pre-administration of glucose but neither of protein nor of fat induced ability of duodenum to respond to orexin-A (240 pmoles/kg × h) with a rise (p<0.01) in bicarbonate secretion. Administration of glucose directly into the luminal perfusate shortly before start of titration was also tested but did, in contrast to preceding gavage of glucose, not induce any response to orexin-A. Feeding significantly increased (p<0.001) enterocyte expression of both orexin receptors.

Conclusion: 

Orexin-A induces duodenal alkaline secretion only in animals pretreated with glucose. The required time interval between glucose exposure and sensitivity to orexin indicates need of gene transcription. It would thus seem likely that gene transcription of duodenal orexin receptors is regulated by a glucose sensitive pathway.