Bromocriptine redirects metabolism and prevents seasonal onset of obese hyperinsulinemic state in Syrian hamsters

Abstract

Bromocriptine redirects metabolism and prevents seasonal onset of the obese hyperinsulinemic state in Syrian hamsters. Metabolic and hormonal effects of bromocriptine were studied in seasonally obese female Syrian hamsters, Mesocricetus auratus. Daily injections of bromocriptine and vehicle (controls) were made at light onset (10:14-h light-dark cycle) for 10 wk. After 9 wk of treatment blood samples were taken every 4 h during a day for assays of hormones, glucose, triglyceride, and fatty acids, and after 10 wk of treatment, tests were carried out to measure insulin-stimulated glucose disposal during a hyperinsulinemic clamp, lipid mobilization (rate of glycerol appearance), protein turnover (lysine flux and deamination), and body composition (deuterium dilution). Bromocriptine reduced percent body fat by 53% and increased percent lean body mass by 8%. It also decreased triglyceride levels by 52% and plasma free fatty acid concentration during the dark-near light onset by 49% and glycerol appearance by 25%. Protein synthesis and catabolism were increased by 62 and 56%, respectively, and deamination of amino acid was decreased by 53% by bromocriptine. Bromocriptine reduced plasma concentration of insulin throughout the day, especially at light onset, by 78% without change in baseline glucose level and markedly decreased steady state plasma glucose (by 40%) during a continuous infusion of insulin and glucose. It also reduced the nocturnal plasma concentration of prolactin by 90%, cortisol by 70%, and thyroid hormones (thyroxine and triiodothyronine) by 50% and dramatically altered the circadian profiles of these hormones and insulin.(ABSTRACT TRUNCATED AT 250 WORDS)

Dopaminergic tone and obesity: an insight from prolactinomas treated with bromocriptine

“…Furthermore, gonadal function was not restored after 1 month of treatment in patients with prolactinomas. The observed reduction in leptin levels at 1 month without change in body weight or BMI may still be indicative of a loss in body fat which has been previously observed in experimental animals (10).…”

Biochemical mechanisms responsible for the attenuation of diabetic and obese conditions in ob/ob mice treated with dopaminergic agonists

“…29,30 Corticosterone is a potent stimulator of lipolysis, hepatic glucose output and lipogenesis, therefore, the substantial reduction of plasma corticosterone induced by the treatment (but not by pair feeding) may contribute to the reductions of these biochemical activities. The drug induced reduction in plasma T 4 concentrations seen in association with decreased body weight gain and increased oxygen consumption may seem paradoxical, however, similar associations have previously been reported with interventions which increase dopamine activities (such as BC treatment in the Syrian hamster 17 and dopamine B-hydroxylase knockout mice. 31 Since thyroid hormones induce hepatic lipogenic malic enzyme activity, and increase glucose output and lipolysis, the reduction of T 4 by BCaSKF (but not by pair feeding) correlates well with the above described treatment effects on metabolism.…”

“…BCaSKF treatment has been shown to increase protein mass in these mice 4 as has bromocriptine in hamsters. 17 The relatively high RQ values presented in Table 2 may be the result of the time of the day that the measurements were taken (at 2 ± 5 h after the onset of light). At this time of day, obaob mice have a low metabolic activity.…”

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.…”