Long-term and Short-term Dopaminergic (Cabergoline) and Antidopaminergic (Sulpiride) Effects on Insulin Response to Glucose, Glucose Response to Insulin, or Both in Horses

Abstract

Dopaminergic drugs, such as those used to treat pituitary pars intermedia dysfunction (PPID) in horses, have been shown to improve insulin sensitivity in other species. It has been suggested that pergolide, used to treat PPID, may enhance insulin sensitivity in resistant horses, although evidence for that remains unclear. Four experiments were conducted herein to determine possible effects of dopaminergic inhibition or stimulation on two indices of insulin sensitivity in horses: the glucose response to insulin (GR2I), administered intravenously (IV) using a fixed dose of recombinant human insulin, and the insulin response to an acute IV infusion of glucose (IR2G). The first experiment tested the short-term effects of sulpiride (in saline; IV) 5 minutes prior to IR2G in insulin-sensitive and insulin-insensitive mares. Experiment 2 tested the effects of a long-term sulpiride protocol (1.5 g intramuscularly [IM] every 5 days for 45 days) on GR2I and IR2G in insulin-sensitive and insulin-insensitive geldings. Experiment 3 tested the short-term effects of 5-mg cabergoline IM on GR2I and IR2G in insulin-sensitive and insulin-insensitive mares. The fourth experiment tested the long-term effects of cabergoline IM on GR2I in insulin-sensitive mares. Results from these experiments revealed that neither increased nor decreased dopaminergic activity, in the long or short term, had any impact on GR2I or IR2G in horses (P > .1), regardless of starting insulin sensitivity status. We conclude that dopaminergic agents have no benefit for treating insulin insensitivity in horses, in spite of a perception of such benefits permeating the industry.