Year of Publication

2009

Degree Name

Doctor of Philosophy (PhD)

Document Type

Dissertation

College

Agriculture

Department

Animal Science

First Advisor

Dr. David Harmon

Abstract

The hormone glucagon-like peptide-2 (GLP-2) is important in the regulation of intestinal growth and blood flow in nonruminant animals. However, no research reports the existence of GLP-2 in ruminants. Therefore, this dissertation examined the existence of GLP-2 and its receptor, their response to physiological stimuli, and its ability to induce gastrointestinal growth and intestinal blood flow in ruminants.

Experiments 1 and 2 established the gastrointestinal distribution of mRNA for proglucagon (the GLP-2 precursor) and the GLP-2 receptor. Furthermore, these experiments determined the effects of changing dietary energy intake on plasma GLP-2 concentrations and proglucagon and GLP-2 receptor mRNA expression. Experiment 3 examined the effect of exogenous bovine GLP-2 on splanchnic blood flow, splanchnic nutrient flux, and gastrointestinal growth.

This research shows that ruminants possess a functional GLP-2 signaling system that responds to nutrient ingestion. Based on observed receptor distribution and growth changes with GLP-2 treatment, GLP-2 targets the small intestine and does not affect forestomach or large intestinal growth. Increases in ileal proglucagon mRNA expression and plasma GLP-2 with increasing energy intake demonstrate that GLP-2 responds to physiologic changes in nutrient intake and can be relevant to feeding practices. Furthermore, observed increases in small intestinal growth and blood flow with GLP-2 suggest that it could substantially affect the capacity of the gastrointestinal tract for nutrient absorption. Modification of GLP-2 through diet could allow for improvements in nutrient utilization and animal productivity. This research also has important implications for use of GLP-2 for human disease therapy as the observed downregulation in the blood flow response to 10-d GLP-2 administration has never been reported in any species prior to this dissertation.

This research systematically characterized and evaluated the potential role of GLP-2 in the control of gastrointestinal growth and splanchnic blood flow in ruminants. While it extends the knowledge of hormonal control of the gastrointestinal tract in ruminants, it also adds crucial information to the larger body of work investigating the actions of GLP- 2. This dissertation research has contributed to the groundwork necessary to enable the use of GLP-2 in improving the health and productivity of a diverse group of mammalian species.

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