EFFICIENCY OF NUTRIENT USE IN CATTLE:IDENTIFICATION OF CRITICAL PHYSIOLOGIC AND GENOMIC REGULATORY PATHWAYS
Title: The glucagon-like peptide 2 pathway may mediate growth and development of the bovine gastrointestinal tract
Submitted to: Journal of Dairy Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: July 8, 2010
Publication Date: November 1, 2010
Citation: Connor, E.E., Baldwin, R.L., Capuco, A.V., Clover, C.M., Ellis, S.E., Sciabica, K.E. 2010. The glucagon-like peptide 2 pathway may mediate growth and development of the bovine gastrointestinal tract. Journal of Dairy Science. 93:5167-5178.
Interpretive Summary: Glucagon-like peptide 2 (GLP-2) is a hormone released from specialized cells in the gastrointestinal tract that has a number of effects on the intestine of mammals, including promotion of growth of the cells lining the intestinal tract, reduction of cell loss from the intestinal tract, and enhancement of intestinal blood flow, nutrient absorption, and barrier function. This hormone has been used effectively as a therapeutic in humans with short-bowel syndrome and in premature infants to improve gut function and nutrient absorption. The regulatory functions of GLP-2 in the gastrointestinal tract of cattle and other ruminant species have not been well studied. In this study, the expression of genes involved in the GLP-2 pathway was evaluated in 9 different regions of the bovine digestive tract using a molecular technique called quantitative PCR. Tissues were collected at slaughter from heifers prior to puberty, mature cows in early, mid, and late lactation, and non-lactating cows. Our findings were consistent with reports of GLP-2 pathway expression and function in other, non-ruminant species and support a functional role of the GLP-2 pathway in the intestinal tract of cattle. Results of this work indicate that GLP-2 therapy of cattle may be useful for improving intestinal function and nutrient absorption, particularly in cases where intestinal function has been compromised, such as parasitic infection or disease.
Glucagon-like peptide 2 (GLP-2), secreted by enteroendocrine cells, has a number of physiological effects on the intestine of monogastric species, including promotion of growth of intestinal epithelium, reduction of epithelial cell apoptosis, and enhancement of intestinal blood flow, nutrient absorption, and epithelial barrier function. The regulatory functions of GLP-2 in the ruminant gastrointestinal tract (GIT) have not been well studied. The objectives of this investigation were to characterize the expression of GLP-2 pathway members throughout the bovine GIT including proglucagon (GCG) mRNA, the parent peptide from which GLP-2 is derived through cleavage by prohormone convertase, prohormone convertase mRNA, GLP-2 receptor (GLP2R) mRNA, and mRNA for dipeptidyl peptidase IV (DPP4), the enzyme that inactivates GLP-2. Gene expression was evaluated in rumen, reticulum, omasum, abomasum, duodenum, jejunum, ileum, cecum, and rectum collected at slaughter from prepubertal heifers, mature cows in early, mid, and late lactation, and non-lactating cows (n = 3 per stage) by quantitative PCR. In addition, mRNA expression of 14 genes involved in nutrient transport, enzyme activity, blood flow, apoptosis, and proliferation were evaluated in the 9 GIT tissues for their association with GCG and GLP2R mRNA expression. Immunohistochemistry was used to localize GLP2R protein expression in tissues of the lower GIT. Results indicated that mRNA expression of GCG, prohormone convertase, GLP2R, and DPP4 varies across the 9 GIT tissues (P < 0.001), with greatest expression in small and large intestines, and generally non-detectable levels in forestomachs. Expression of DPP4 and GLP2R mRNA varied by developmental stage or lactational state (P < 0.05) in intestinal tissues. Expression of GCG or GLP2R mRNA was correlated with molecular markers of proliferation, apoptosis, blood flow, enzyme activity, and urea transport, depending on the tissue examined, which supports involvement of GLP-2 in these physiological processes in ruminant GIT. The GLP2R protein expression was confirmed in bovine GIT in intestinal crypts, which is consistent with the distribution in monogastric species. Our findings support a functional role of the GLP-2 pathway in bovine GIT and the potential use of GLP-2 to improve intestinal function and nutrient absorption in ruminants.