Effects of bromocriptine on glucose and insulin dynamics in normal and insulin dysregulated horses

Authors: LOOS, CAROLINE - University Of Kentucky; URSCHEL, KRISTINE - University Of Kentucky; VANZANT, ERIC - University Of Kentucky; OBERHAUS, E. - Louisiana State University; BOHANNAN, ADAM - University Of Kentucky; Klotz, James; MCLEOD, KYLE - University Of Kentucky

Submitted to: Frontiers in Veterinary Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/9/2022
Publication Date: 5/31/2022
Citation: Loos, C.M., Urschel, K.L., Vanzant, E.S., Oberhaus, E.L., Bohannan, A.D., Klotz, J.L., Mcleod, K.M. 2022. Effects of bromocriptine on glucose and insulin dynamics in normal and insulin dysregulated horses. Frontiers in Veterinary Science. 9. Article 889888. https://doi.org/10.3389/fvets.2022.889888.
DOI: https://doi.org/10.3389/fvets.2022.889888

Interpretive Summary: Insulin is a key hormone in the regulation of carbohydrate, fat, and protein metabolism that is involved with the absorption of glucose from the blood into cells. A common clinical problem in the equine industry is the malfunction of insulin regulation and sensitivity. This is associated with laminitis - a crippling inflammation and damage of the tissue between the hoof and the underlying bone making walking and standing extremely painful. Few science-based pharmaceutical treatments currently exist to treat horses with this condition. Bromocriptine, a synthetic ergot alkaloid similar to compounds responsible for fescue toxicosis, has been shown in other animal species to improve insulin sensitivity. This study sought to investigate the effects of bromocriptine on glucose and insulin changes in horses with and without insulin regulation issues. Results demonstrated that bromocriptine treatment in the equine model caused a decrease in both groups of horses. This is in contrast to human and rodent models, but is similar to results in cattle. Interestingly, it was also noted that the bromocriptine treatment may alter feed preference away from high caloric density feedstuffs. These findings are of interest to those in the equine industry as well as other livestock producers and researchers interested and/or concerned about ergot alkaloids.

Technical Abstract: The objectives of the study were to study the effects of the synthetic ergot alkaloid (EA), bromocriptine, on glucose and lipid metabolism in insulin dysregulated (ID, N=7) and non-ID (N=8) mares. Horses were individually housed and fed timothy grass hay and 2 daily concentrate meals so that the total diet provided 120 % of daily DE requirements for maintenance. All horses were given intramuscular bromocriptine injections (0.1 mg/kg BW) every 3 days for 14 days. Before and after 14 days of treatment horses underwent a combined glucose-insulin tolerance test (CGIT) to assess insulin sensitivity and a feed challenge (1g starch/kg BW from whole oats) to evaluate postprandial glycemic and insulinemic responses. ID horses had higher basal plasma concentrations of insulin (P = 0.01) and triglycerides (P = 0.02), and lower concentrations of adiponectin (P = 0.05) compared with non-ID horses. The CGIT response curve showed that ID horses had slower glucose clearance rates (P = 0.02) resulting in a longer time in positive phase (P = 0.03) and had higher insulin concentrations at 75 min (P = 0.0002) compared with non-ID horses. Glucose (P = 0.02) and insulin (P = 0.04) responses to the feeding challenge were lower in non-ID compared to ID horses. Regardless of insulin status, bromocriptine administration increased hay intake (P = 0.03) and decreased grain (P < 0.0001) and total DE (P = 0.0002) intake. Bromocriptine treatment decreased plasma prolactin (P = 0.0002) and cholesterol (P = 0.10) and increased (P = 0.02) adiponectin concentrations in all horses. Moreover, in both groups of horses, bromocriptine decreased glucose clearance rates (P = 0.02), increased time in positive phase (P = 0.04) of the CGIT and increased insulin concentrations at 75 min (P = 0.001). The postprandial glycemic (P = 0.01) and insulinemic (P = 0.001) response following the oats meal was lower after bromocriptine treatment in all horses. In conclusion, in contrast to data in humans and rodents, bromocriptine treatment reduced insulin sensitivity in all horses, regardless of their insulin status. These results indicate that the physiological effects of EA might be different in horses compared to other species. Moreover, because bromocriptine shares a high degree of homology with natural EA, further investigation is warranted in horses grazing endophyte-infected grasses.