Bromocriptine improves glucose tolerance independent of circadian timing, prolactin, or the melanocortin-4 receptor.

doi:10.1152/ajpendo.00325.2019

Paper

Bromocriptine improves glucose tolerance independent of circadian timing, prolactin, or the melanocortin-4 receptor.

Published Dec 3, 2019 · Sarah N. Framnes-DeBoer, Ellen Bakke, Suma Yalamanchili

American journal of physiology. Endocrinology and metabolism

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12

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Abstract

Bromocriptine, a dopamine D2 receptor agonist originally used for the treatment of hyperprolactinemia, is largely successful in reducing hyperglycemia and improving glucose tolerance in type 2 diabetics. While the mechanism behind bromocriptine's effect on glucose intolerance is unclear, here we test three hypotheses: that bromocriptine may exert its effects on glucose metabolism by 1) decreasing prolactin secretion, 2) indirectly increasing activity of key melanocortin receptors in the CNS, or 3) improving/restoring circadian rhythms. Using a diet-induced obese (DIO) model, we establish that a 2-week treatment of bromocriptine is robustly effective at improving glucose tolerance in mice. We then demonstrate that bromocriptine is effective at improving the glucose tolerance of DIO prolactin-deficient mice, pointing to bromocriptine's ability to effect glucose tolerance independently of prolactin. Similarly, bromocriptine is effective at improving the glucose tolerance of mice lacking the melanocortin-4 receptor (MC4R). Finally, we test bromocriptine's dependence on the circadian system by testing its effectiveness in environmental (e.g. repeated shifts to the light:dark cycle) and genetic (e.g. the Clock mutant mouse) models of circadian disruption. For both models, bromocriptine was effective at improving glucose tolerance, indicating that a functional or well-aligned endogenous clock is not necessary for bromocriptine's effects on glucose metabolism. Taken together, these results do not support the role of prolactin, MC4R, or the circadian clock as integral to bromocriptine's underlying mechanism. Instead, we find that bromocriptine is a robust diabetic treatment and resilient to genetically induced obesity, diabetes, and circadian disruption.

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Animal Study

Study Snapshot

Bromocriptine improves glucose tolerance independently of prolactin, melanocortin-4 receptor, or circadian clock, making it a robust diabetic treatment and resilient to genetically induced obesity, diabetes, and circadian disruption.

PopulationOlder adults (50-71 years)

Sample size24

MethodsObservational

OutcomesBody Mass Index projections

ResultsSocial networks mitigate obesity in older groups.

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Paper

Bromocriptine improves glucose tolerance independent of circadian timing, prolactin, or the melanocortin-4 receptor.

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References

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Vertical sleeve gastrectomy improves ventilatory drive and chemosensitivity in obesity hypoventilation syndrome through a leptin-dependent mechanism, highlighting physiological components of obesity as key drivers in the disorder.

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Dopamine agonist therapy, such as bromocriptine-QR, shows modest improvements in glycemic parameters, cholesterol, and weight in type 2 diabetes patients, with a favorable cardiovascular risk reduction.

Does bromocriptine play a role in decreasing oxidative stress for early weaned programmed obesity?

Early weaning with bromocriptine can improve offspring's redox status and may prevent liver damage during adulthood, despite obesity and glucose homeostasis dysfunction.

Angiotensin-converting enzyme inhibition reduces food intake and weight gain and improves glucose tolerance in melanocortin-4 receptor deficient female rats

Inhibiting angiotensin-converting enzyme (ACE) in melanocortin-4 receptor deficient female rats leads to rapid weight loss and improved glucose tolerance without requiring melanocortin-4 receptor signaling.

The role of bromocriptine-QR in the management of type 2 diabetes expert panel recommendations.

Bromocriptine-QR shows potential in improving insulin sensitivity and reducing hepatic glucose output in type 2 diabetes patients, but its safety and efficacy in common diabetes regimens require further research.

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