Bromocriptine-Induced Hyperglycemia in Nonobese Diabetic Mice: Kinetics and Mechanisms of Action

Abstract

■ AbstractThe effects of bromocriptine (10 mg/kg), known to inhibit prolactin secretion and lower autoimmune processes, were studied on glucose homeostasis in non-fasted non-obese diabetic mice, a spontaneous model of type 1 diabetes. Hyperglycemia was observed 120 and 240 min after i.p. but not s.c. injection. Bromocriptine administration i.p. led to rapid and marked hyperglycemia characterized by sexual dimorphism with males having higher glycemia than females. Bromocriptine induced a rapid but transient decrease in insulinemia in males only and biphasic increases in glucagon levels and a sustained stimulatory effect on circulating corticosterone in both sexes. Bromocriptine-induced hyperglycemia involved D2-dopaminergic receptors, as demonstrated by the inhibitory effect of the D2-dopamine antagonist, metoclopramide (10 mg/kg). Simultaneous injection of bromocriptine and metoclopramide also blocked the rise in blood corticosterone. In conclusion, by inducing hyperglycemia, i.p. bromocriptine administration to prediabetic autoimmune mice may counteract its beneficial antiimmunostimulatory effects.

Bromocriptine Administration Reduces Hyperphagia and Adiposity and Differentially Affects Dopamine D2 Receptor and Transporter Binding in Leptin-Receptor-Deficient Zucker Rats and Rats with Diet-Induced Obesity

“…This view is further supported by a recent study that examined BC-induced hyperglycemia and blood corticosterone increases in nonobese diabetic mice [57]. This study also utilized a 10 mg/kg dose of BC and concluded that the BC-induced hyperglycemia and blood corticosterone increases involved D2R since concurrent administration of 10 mg/kg of the D2R antagonist metoclopramide blocked these effects [57]. Another recent study also selectively utilized a 10 mg/kg dosing regimen in combination with Hypericum perforatum (a natural antioxidant) to show reduced 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP)-induced neurotoxicity in mice [58].…”

“…Although we cannot directly argue for the results that we report as being D2R and DAT dependent, the fact that we do report changes in D2R and DAT binding which coincide with a reduction in obesity and NAFLD markers using this specific dose and treatment regimen is suggestive of the potential involvement of D2R and DAT in these effects. This view is further supported by a recent study that examined BC-induced hyperglycemia and blood corticosterone increases in nonobese diabetic mice [57]. This study also utilized a 10 mg/kg dose of BC and concluded that the BC-induced hyperglycemia and blood corticosterone increases involved D2R since concurrent administration of 10 mg/kg of the D2R antagonist metoclopramide blocked these effects [57].…”

Leptin increases striatal dopamine D2 receptor binding in leptin‐deficient obese (ob/ob) mice

“…In humans, reports of changes in peripheral glucose and insulin concentrations after administration of D2R agonists (Scranton et al, 2007) and antagonists (Pezzarossa et al, 1986) further supports this view. In particular, the D2R agonist bromocriptine currently holds promise as an effective diabetes medication (Durant et al, 2007; Scranton et al, 2007). …”

Fetal Pancreas Transplants Are Dependent on Prolactin for Their Development and Prevent Type 1 Diabetes in Syngeneic but Not Allogeneic Mice

“…To address this question, we treated mice with bromocriptine, an inhibitor of prolactin production (25,26). The higher level of insulin in transplants of female compared with male recipients at 3 weeks was confirmed again in control mice receiving the placebo.…”