Aims: 

Overnight fasting abolishes the duodenal mucosal bicarbonate responses to appetite-re lated peptides like orexin-A and apelin-13 but not those to melatonin or VIP. Incretins are major regulators of insulin secretion and gastrointestinal motility. We have thus investigated effects of GIP and GLP-1 on the duodenal alkaline secretion in fed and fasted rats. Effects of glucagon like peptide-2 (GLP-2) and pancreatic glucagon were studied for comparison.

Methods: 

Overnight fasted or continuously fed Lewis x Dark Agouti rats were anesthetized and mucosal bicarbonate secretion titrated in situ. Peptides were administered to the duodenum by close intra-arterial infusion. Total RNA was extracted from mucosal specimens and peptide receptor expressions measured by quantitative real-time PCR. Blood glucose was measured at the start and end of experiments.

Results: 

GIP infused at rates of 60, 240 and 600 pmol kg^-1 h^-1 induced a dose-dependent rise (p< 0.01) in bicarbonate secretion, and fasting abolished this secretory response. GLP-1 caused a significant rise in the duodenal secretion but higher doses were required (p< 0.05 at 2400 pmol kg^-1 h^-1). As found with GIP, stimulation by GLP-1 occurred only in fed animals. Glucagon (600 pmol kg^-1 h^-1) induced secretory responses in fasted (p< 0.01) as well as fed (p< 0.05) animals. GLP-2 (600 pmol kg^-1 h^-1) did not affect the duodenal secretion. Fasting did not significantly affect GIP and GLP-1 but increased GLP-2 and glucagon receptor expressions. Glucagon, but not GIP or GLP-1, prevented the decline in blood glucose concentration observed in control animals.

Conclusion: 

The incretins GIP and GLP-1 stimulate duodenal electrolyte secretion. Stimulation is feeding-dependent in spite of normal mucosal receptor expressions.