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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 (. repeated shifts to the light:dark cycle) and genetic (. the 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.
This article was published in the following journal.
Name: American journal of physiology. Endocrinology and metabolism
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