Associations between feeding and glucagon-like peptide-2 in healthy ponies

Background: Gastrointestinal peptides, such as glucagon-like peptide-2 (GLP-2), could play a direct role in the development of equine hyperinsulinaemia. Objectives: To describe the secretory pattern of endogenous GLP-2 over 24 h in healthy ponies and determine whether oral administration of a synthetic GLP-2 peptide increases blood glucose or insulin responses to feeding. Study Design: A cohort study followed by a randomised, controlled, cross-over study. Methods: In the cohort study, blood samples were collected every 2 h for 24 h in seven healthy ponies and plasma [GLP-2] was measured. In the cross-over study, 75 mu g/kg bodyweight of synthetic GLP-2, or carrier only, was orally administered to 10 ponies twice daily for 10 days. The area under the curve (AUC(0-3h)) of postprandial blood glucose and insulin were determined before and after each treatment. Results: Endogenous [GLP-2] ranged from <0.55 to 1.95 +/- 0.29 [CI 0.27] ng/mL with similar peak concentrations in response to meals containing 88-180 g of non-structural carbohydrate, that were similar to 4-fold higher (P < 0.001) than the overnight nadir. After GLP-2 treatment peak plasma [GLP-2] increased from 1.1 [0.63-1.37] ng/mL to 1.54 [1.1-2.31] ng/mL (28.6%; P = 0.002), and AUC(0-3h) was larger (P = 0.01) than before treatment. The peptide decreased (7%; P = 0.003) peak blood glucose responses to feeding from 5.33 +/- 0.45 mmol/L to 5.0 +/- 0.21 mmol/L, but not AUC(0-3h) (P = 0.07). There was no effect on insulin secretion. Main Limitations: The study only included healthy ponies and administration of a single dose of GLP-2. Conclusions: The diurnal pattern of GLP-2 secretion in ponies was similar to other species with no apparent effect of daylight. Although GLP-2 treatment did not increase post-prandial glucose or insulin responses to eating, studies using alternative dosing strategies for GLP-2 are required.