Short-Chain Fatty Acids and Glucagon -Like Peptide-2 Enhance Intestinal Development and Adaptation
Bartholome, Anne Louise
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https://hdl.handle.net/2142/84937
Description
Title
Short-Chain Fatty Acids and Glucagon -Like Peptide-2 Enhance Intestinal Development and Adaptation
Author(s)
Bartholome, Anne Louise
Issue Date
2004
Doctoral Committee Chair(s)
Kelly A. Tappenden
Department of Study
Nutritional Sciences
Discipline
Nutritional Sciences
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Keyword(s)
Health Sciences, Human Development
Language
eng
Abstract
In 2002, 43% of the ∼470,822 preterm infants were born at a low birth weight. These infants have a higher risk for intestinal dysfunctions indicating the use of total parenteral nutrition (TPN) to meet their nutritional needs. Despite its benefits, TPN is associated with many complications; hence, treatments aimed at minimizing the need for TPN are necessary. Glucagon-like peptide-2 (GLP-2) may be a therapeutic agent as it reduces TPN associated atrophy and increases enzyme and transporter activity. To examine this, we coinfused GLP-2 with TPN and found increased ileal mRNA and protein abundance of the brush border sodium-dependent glucose cotransporter, SGLT-1. However, the minimum effective dose that is necessary to enhance intestinal function is unknown. Therefore, GLP-2 was coinfused with TPN at three physiological doses: low, moderate and high. Results show that the mRNA abundance of the basolateral sodium-independent glucose transporter, GLUT2, was increased to enteral levels by all GLP-2 doses. Furthermore, the low GLP-2 dose increased brush border membrane (BBM) protein abundance of GLUT2. This increase corresponded with an increase in glucose uptake, indicating that GLP-2 may be enhancing neonatal intestinal function through the translocation of GLUT2 from the basolateral to the BBM. Systemic short-chain fatty acids and dietary fiber are reported to stimulate the secretion of GLP-2. Therefore, we supplemented TPN with butyrate and found increases in structural adaptation. The most marked effects were in the intestinal epithelium, with increased crypt-villus architecture resulting from increased proliferation and decreased apoptosis. Additionally, butyrate increased the plasma GLP-2 concentration through a rapid and specific increase in ileal and colonic mRNA abundance of proglucagon, the gene that encodes GLP-2. Thus, GLP-2 may mediate the intestinotrophic effects of butyrate. Further evidence for the intestinotrophic effects of GLP-2 was investigated using a degradation-resistant GLP-2 analog, teduglutide, in adult patients with short-bowel syndrome. Teduglutide increased crypt-villus architecture, glucose and glutamine transport and the protein expression of nutrient transporters. The provision of GLP-2 and supplementation of TPN with butyrate, which augments endogenous levels of GLP-2, may benefit patients with intestinal dysfunctions by maximizing their intestinal absorptive capacity, thereby enabling them to successfully transition to enteral feedings.
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