Regulation of intestinal nutrient uptake by glucagon-like peptide-1 in rats

Date

1998-08

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Publisher

Texas Tech University

Abstract

Glucagon-like peptide-1 (GLP-1) is a peptide derived from the prohormone proglucagon and is secreted primarily from the L-cells of the ileum. The major bioactive form of GLP-1 is truncated GLP-1 (tGLP-1). tGLP-1 is shortened by 6 amino acids from the N-terminus and has a C-terminal amidation. Food and water intake are both inhibited by tGLP-1, and its action as an incretin hormone (a hormone that stimulates insulin release in the presence of elevated blood glucose concentrations) is believed to be its most biologically important function. Nevertheless, many other functions for tGLP-1 have been proposed in many different tissues. Oxyntomodulin is co-secreted with tGLP-1 from the L-cells, and both peptides share sequence homology with glucagon. Moreover, both oxyntomodulin and glucagon increase active glucose transport across the brush-border membrane of the small intestine. Based on this information, I tested the hypothesis that tGLP-1 might also regulate intestinal nutrient uptake. Male Sprague-Dawley rats were infused with different doses of synthetic rat tGLP-1 transport rates of several representative nutrients (proline, alanine, glucose, and finctose) measured using an everted intestinal sleeve method. Proline and alanine transport were unaffected, and we were surprised to find that glucose uptake was either unaffected or slightly inhibited by the infusions. Equally surprising, however, was that fructose transport was stimulated strongly in the proximal intestine, and the animal's overall, daily capacity to transport fructose was also stimulated. These results along with the fact that the intestinal morphology did not change during the course of the experiment provide the first evidence of tGLP-1 as a hormonal signal regulating fructose transport.

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Keywords

Glucagon-like peptide 1, Fructose, Intestinal absorption, Peptide hormones

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