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Am J Physiol Endocrinol Metab (May 9, 2006). doi:10.1152/ajpendo.00099.2006
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Submitted on March 2, 2006
Accepted on May 2, 2006

The release of GLP-1 and ghrelin, but not GIP and CCK, by glucose is dependent upon the length of small intestine exposed

Tanya J Little1, Selena Doran1, James Meyer2, Andre Smout3, Deirdre G O'Donovan1, Keng-Liang Wu1, Karen L. Jones4, Judith Wishart1, Christopher K Rayner1, and Christine Feinle-Bisset1*

1 Medicine, Royal Adelaide Hospital, University of Adelaide, Adelaide, South Australia, Australia
2 Santa Monica, California, United States; Medicine, Royal Adelaide Hospital, University of Adelaide, Adelaide, South Australia, Australia
3 Gastroenterology, University Hospital, Utrecht, Netherlands
4 Department of Medicine, University of Adelaide, Adelaide, Australia

* To whom correspondence should be addressed. E-mail: christine.feinle{at}adelaide.edu.au.

Previous observations suggest that glucagon-like peptide-1 (GLP-1) is released into the bloodstream only when dietary carbohydrate enters the duodenum at rates that exceed the absorptive capacity of the proximal small intestine to contact GLP-1 bearing mucosa in more distal bowel. The aims of this study were to determine the effects of modifying the length of small intestine exposed to glucose on plasma concentrations of GLP-1, and also glucose-dependent insulinotropic peptide (GIP), insulin, cholecystokinin (CCK) and ghrelin, and antropyloric pressures. Glucose was infused at 3.5 kcal/min into the duodenum of eight healthy males (age: 18 - 59 years) over 60 min. On the first day into an isolated 60 cm segment of the proximal small intestine ("short segment infusion"); on the second day, the same amount of glucose was infused with access to the entire small intestine ("long segment infusion"). Plasma GLP-1 increased and ghrelin decreased (P < 0.05 for both) during the "long", but not the "short", segment infusion. By contrast, increases in plasma CCK and GIP did not differ. The rises in blood glucose and plasma insulin were greater during the "long", when compared with the "short", segment infusion (P < 0.05). During the "long", but not the "short", segment infusion antral PWs were suppressed (P < 0.05). Isolated pyloric pressure waves and basal pyloric pressure were stimulated on both days. In conclusion, the release of GLP-1 and ghrelin, but not CCK and GIP, is dependent upon greater than 60 cm of the intestine being exposed to glucose.




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