Background: Insulin dysregulation (ID) is the most important risk factor for the development of laminitis in horses and therapies to control it are needed.
Hypothesis/objectives: To assess the effects of a single dose of the synthetic GLP-1 analog exenatide on postprandial insulin dynamics. We hypothesized that exenatide would improve insulin sensitivity and lower postprandial blood insulin concentrations.
Study design: Randomized, crossover, experimental study.
Animals: Six horses (3 mares, 3 geldings; 2 with normal insulin regulation [NIR] and 4 with mild ID).
Methods: Horses completed both study arms: subcutaneous administration of exenatide (or no treatment) 30 min before an oral sugar test (0.15 ml/kg of Karo Syrup). Blood samples obtained over 240 min were assayed for glucose, insulin, lactate, c-peptide and total GLP-1. The area under the curve (AUC) was calculated using the trapezoidal rule. Insulin sensitivity (SI) was estimated using a mathematical model.
Results: Exenatide resulted in a postprandial decrease of 20% (effect size: 2673 µU·min/ml; 95% CI: 900 - 4446 µU·min/ml; P = 0.003) in AUC of plasma insulin (control; mean AUC insulin: 11,989 µU·min/ml; 95% CI: 9673 - 14,305 µU·min/ml, exenatide; mean AUC insulin: 9316 µU·min/ml; 95% CI: 7430 - 11,202 µU·min/ml). Exenatide resulted in an approximately threefold increase (effect size: 5.56 10-4· µU/ml-1·min-1; 95% CI: 0.95 - 10.1 10-4· µU/ml-1·min-1; P = 0.02) in estimated insulin sensitivity (control mean SI: 1.93 10-4· µU/ml-1·min-1; 95% CI: 0.005 - 3.86 10-4·µU/ml-1·min-1 vs. exenatide mean SI: 7.49 10-4· µU/ml-1·min-1; 95% CI: 3.46 - 11.52 10-4· µU/ml-1·min-1).
Conclusions: The decrease in insulin response to carbohydrates was due to an increase in whole-body insulin sensitivity. GLP-1 agonists may have therapeutic potential for ID in horses.
Keywords: Equine Metabolic Syndrome (EMS); Horse; Insulin dysregulation; Insulin secretion; Insulin sensitivity.
© 2022. The Author(s).