Recent studies have shown that close intra-arterial infusion of low doses of the appetite-regulating peptide orexin-A markedly increases duodenal mucosal bicarbonate secretion. Interestingly, short (overnight) food-deprivation decreases enterocyte expression of orexin receptors and abolishes the secretory response as well as orexin-A induced intracellular calcium signaling (Bengtsson et al. 2009). We have continued our studies of satiety-regulating peptides, examining effects of the incretins glucose-dependent insulinotropic polypeptide (GIP) and glucagon like peptide-1 (GLP-1) on the duodenal secretion in fed and overnight fasted animals.

Methods: 

Lewis x Dark Agouti rats had free access to water and, unless fasted overnight, free access to food. Animals were anesthetized (thiobarbiturate, 120 mg/kg) and a segment of proximal duodenum with intact blood supply cannulated in situ. Mucosal bicarbonate secretion (pH stat) was continuously recorded and peptides were administered to the duodenum by close intra-arterial infusion.

Results: 

Intra- arterial infusion of GIP (60–600 pmol/kg, h) caused dose- dependent increases in duodenal bicarbonate secretion in fed animals (p<0.01) but not in fasted animals (p>0.05). The same doses of GLP-1 (60–600 pmol/kg, h) did not affect the duodenal secretion but a higher dose (6000 pmol/kg, h); GLP-1 induced a slight increase (p<0.05) in the secretion.

Conclusions: 

GIP and at higher doses GLP-1, stimulate duodenal bicarbonate secretion in fed but not in overnight fasted rats. Studies of intestinal secretion, and in particular of effects of appetite- regulating hormones, require particular evaluation with respect to feeding status. Reference: Bengtsson M.W., Mäkelä K., Herzig K.H. & Flemström G. 2009. Am J Physiol 296: G651-G658.