Bromocriptine Alters Hormone Rhythms and Lipid Metabolism in Swine

Abstract

Hormones, metabolites and activities involved in lipid synthesis were assayed in pigs made leaner by bromocriptine treatment. Market size female swine were allowed free access to food under natural lighting conditions and implanted with bromocriptine pellets designed to release 10 mg/pig/day for 28 days in an effort to inhibit prolactin secretion. Between the 2nd and 3rd week of treatment, plasma samples were obtained from each group at 4-hour intervals throughout the day for assays of prolactin, cortisol, insulin, triglyceride, cholesterol and glucose concentrations. Twenty-eight or thirty days after the implantations, all animals were sacrificed for determinations of backfat thickness and insulin binding in the liver. At sacrifice, bromocriptine treatment reduced backfat thickness by 14% and insulin binding to partially purified hepatic membranes by 39% compared with control values. At 14 days following implantations, there were dramatic daily variations in plasma cortisol and prolactin levels in the control pigs and these rhythms were markedly altered in phase and amplitude in the bromocriptine-treated pigs. Bromocriptine reduced by 45, 20 and 13% the high levels of triglyceride, glucose, and cholesterol, respectively, that were found in control pigs near sunset. Plasma insulin concentrations did not vary during the day in control pigs and bromocriptine did not influence the insulin levels. The findings support important roles for a temporal synergism of cortisol and prolactin rhythms in maintaining hepatic lipogenic responsiveness to insulin. Bromocriptine treatment alters these hormonal relations and reduces lipid synthesis.

Bromocriptine: a novel approach to the treatment of type 2 diabetes.

“…The present results are consistent with data obtained in many vertebrate species (11)(12)(13), including humans (15,17), which have shown that bromocriptine administration improves glucose tolerance in nondiabetic obese animals and humans. Moreover, the present findings extend previous observations to obese patients with type 2 diabetes and demonstrate for the first time in humans the clinical usefulness of bromocriptine in the treatment of individuals with type 2 diabetes.…”

“…It has been proposed that bromocriptine can reverse many of the metabolic alterations associated with obesity by resetting central (hypothalamic) circadian organization of monoamine neuronal activi-Pijl and Associates ties. Indeed, bromocriptine, if administered systemically (9,(11)(12)(13) or into the cerebral ventricle (14) during the early hours of the light cycle, prevents or reverses seasonal fattening, insulin resistance, and decreased endogenous (hepatic) glucose production in mammals. Moreover, timed bromocriptine treatment decreased body weight and improved glucose tolerance in obese individuals who were instructed to follow a hypocaloric diet (15).…”

Bromocriptine-QR therapy for the management of type 2 diabetes mellitus: developmental basis and therapeutic profile summary

“…Moreover, numerous studies have consistently demonstrated the ability of such circadian-timed daily administration of bromocriptine (systemic or intracerebroventricular) to markedly reduce insulin resistance (particularly during the postprandial state [125,126], in agreement with its ability to improve VMH hypothalamic fuel-sensing mechanisms as described above), hyperinsulinemia and/or glucose intolerance without raising the plasma insulin level, in a variety of animal models of IRS including seasonal insulin-resistant hamsters, SHRs, high-fat fed rats, genetically leptin-deficient ob/ob mice, fattened pigs, and high-fat fed dogs [86,124,[126][127][128][129][130][131][132]. As a composite, these animal studies provide evidence that timed bromocriptine treatment improves dysglycemia by improving (postprandial) insulin action in the liver and/or peripheral insulin-sensitive tissues (e.g.…”

Intracerebroventricular Administration of Bromocriptine Ameliorates the Insulin-Resistant/Glucose-Intolerant State in Hamsters

“…Bromocriptine, a potent pleotropic neuromodulator [6], has been shown in a variety of animals, including humans, to improve glucose intolerance, insulin resistance and hyperinsulinemia, as well as to reduce body fat stores [7, 8, 9]. Bromocriptine is a dopamine D 2 receptor agonist, adrenergic α 1 antagonist, α 2 agonist and serotonin antagonist [6].…”

“…Bromocriptine is a dopamine D 2 receptor agonist, adrenergic α 1 antagonist, α 2 agonist and serotonin antagonist [6]. As a result, the molecule is strongly sympatholytic and when administered in the morning near light onset can improve abnormalities in numerous endocrine functions associated with diabetes in animals and man [7, 8, 9, 10, 11]. The ability of bromocriptine to reduce insulin resistance is associated with marked reductions in lipolysis and hepatic glucose production [12], which may be a function of bromocriptine’s dopaminergic sympatholytic activity.…”