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

Valencia, Nicole Arana; Thompson, Donald L.; Oberhaus, E.L.

doi:10.1016/j.jevs.2017.10.008

Cited by 6 publications

(7 citation statements)

References 31 publications

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“…Despite an increase in plasma adiponectin concentrations, insulin sensitivity was decreased in both ID and non-ID horses after 14 days of bromocriptine treatment. Previous work in both non-ID and ID horses reported no difference in insulin sensitivity after treatment with other dopamine agonists, including pergolide mesylate and cabergoline ( 6 , 7 ). This suggest that the physiological effects of synthetic EA are not only species-specific, but might also depend on their affinity and action on particular dopamine receptors.…”

Section: Discussionmentioning

confidence: 82%

“…It is important to note this was an uncontrolled study with use of privately owned horses and the dosage of pergolide administration and management varied between horses, making conclusive inferences difficult. Repeated intramuscular injections with another dopamine receptor agonist, cabergoline, for 45 days did not alter the insulin response to an intravenous glucose infusion ( 7 ). However, that study did not assess glucose clearance rate after exogenous glucose and insulin infusion or the insulin response to an oral glycemic challenge.…”

Section: Introductionmentioning

confidence: 99%

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Effects of Bromocriptine on Glucose and Insulin Dynamics in Normal and Insulin Dysregulated Horses

et al. 2022

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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 two 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 (1 g 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.

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Section: Discussionmentioning

confidence: 82%

Section: Introductionmentioning

confidence: 99%

Effects of Bromocriptine on Glucose and Insulin Dynamics in Normal and Insulin Dysregulated Horses

et al. 2022

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“…In accordance with previous reports ( 10 , 11 , 17 ), horses initially received treatment with ERC as an intramuscular injection (5 mg/mL) 2 at a “high” dose of 0.01 mg/kg (HDERC). Some horses were reported by owners to experience in appetence at this higher dose, and prompting a change in the practice protocol to use a “low” dose of 0.005 mg/kg (LDERC) for subsequent cases in an attempt to mitigate issues with appetite reduction.…”

Section: Methodsmentioning

confidence: 77%

“…Cabergoline is a dopaminergic agonist that has the same mechanism of action as pergolide but is available as an extended-release intramuscular injection, alleviating the need for daily oral administration of medication ( 10 , 11 ). For several decades, cabergoline was used to treat functional pituitary adenomas in humans, including cases refractory to pergolide therapy, as it has a high affinity for dopaminergic receptors in the hypothalamus and pituitary gland ( 12 – 16 ).…”

Section: Introductionmentioning

confidence: 99%

“…For several decades, cabergoline was used to treat functional pituitary adenomas in humans, including cases refractory to pergolide therapy, as it has a high affinity for dopaminergic receptors in the hypothalamus and pituitary gland ( 12 – 16 ). Previous studies in horses have investigated the effects of cabergoline on prolactin, MSH and insulin concentrations ( 10 , 11 , 17 ) and shown that these hormones have reduced consistent with the drug having an inhibitory effect on both melanotrophs and lactotrophs in the equine pituitary gland.…”

Section: Introductionmentioning

confidence: 99%

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Retrospective assessment of the use of extended-release cabergoline in the management of equine pituitary pars intermedia dysfunction

Sundra,

Kelty,

Rossi

et al. 2024

Front. Vet. Sci.

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IntroductionDopaminergic agonists are accepted as the most effective treatment for pituitary pars intermedia dysfunction. However, some horses are refractory to daily oral pergolide, the recommended registered treatment. Extended-release cabergoline (ERC) injection may offer an alternative. The objective of this retrospective case series was to describe clinical and endocrinological responses to ERC.MethodsMedical records of horses treated with weekly intramuscular injections of ERC (5 mg/mL, BOVA Aus) at either 0.01 mg/kg (high dose, HD) (n = 10) or 0.005 mg/kg (low dose, LD) (n = 30) were reviewed. Short-term ACTH responses were assessed at 5–8 days using a Wilcoxon signed ranked test. Longer-term ACTH responses (30 to 365 days) were assessed using generalised estimating equations.ResultsFive to eight days after the first dose of LDERC, median adrenocorticotropic hormone (ACTH) concentration was lower (p = 0.001), changing from 153 pg/mL (IQR: 78, 331) to 57 pg/mL (IQR: 30, 102). With HDERC, median ACTH concentration was also 153 pg/mL (IQR: 96, 185) before and then 56 pg/mL (IQR: 29, 86) after 5–8 days of treatment (p = 0.047). Over 12 months of treatment, ACTH concentration ranged from 14 to >1,250 pg/mL (median: 51 pg/mL) in horses treated with LDERC and 20 to 472 pg/mL (median: 50 pg/mL) in horses treated with HDERC. Measurements remained above the seasonal reference range in 39.3 and 52.3% of horses treated with LDERC and HDERC, respectively. Clinical improvement was reported by owners in 78.3 and 100% of horses treated with LDERC and HDERC, respectively. Partial, self-limiting inappetence was reported in 30.0% of LDERC and 60% HDERC cases. Seven horses exhibited lethargy (5 LDERC, 2 HDERC). Insulin concentrations measured 30 days post-ERC treatment were no different from baseline.DiscussionClinical and endocrinological responses were consistent with results of previous reports of oral pergolide treatment. Weekly injection of ERC may be an effective alternative to pergolide; the 0.005 mg/kg dose appeared to be as effective, with less risk of inappetence, than the 0.01 mg/kg dose that has been reported previously.

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Physiological and metabolic effects of short-term dopamine reduction in healthy horses using a tyrosine hydroxylase inhibitor (alpha-methyl-para-tyrosine)

Galinelli,

Bamford,

Erdody

et al. 2024

Domestic Animal Endocrinology

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

Cited by 6 publications

References 31 publications

Effects of Bromocriptine on Glucose and Insulin Dynamics in Normal and Insulin Dysregulated Horses

Effects of Bromocriptine on Glucose and Insulin Dynamics in Normal and Insulin Dysregulated Horses

Retrospective assessment of the use of extended-release cabergoline in the management of equine pituitary pars intermedia dysfunction

Physiological and metabolic effects of short-term dopamine reduction in healthy horses using a tyrosine hydroxylase inhibitor (alpha-methyl-para-tyrosine)

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