Effects of chronic bromocriptine (CB-154) treatment on the plasma glucose and insulin secretion response to neurocytoglucopenia in rats

Abstract

Neurocytoglucopenia has been reported to increase both parasympathetic and sympathetic tone with a predominant effect on the latter, which accounts for the major effect of plasma hyperglycemia and the inhibition of insulin secretion. The aim of this study was to determine the effects of chronic treatment with bromocriptine (0.4 mg/100 g body wt per day), a potent sympatholytic D2-dopaminergic agonist, on hyperglycemia and insulin secretion in response to neurocytoglucopenia induced by 2-deoxy-D-glucose (2DG). After 2 weeks of bromocriptine treatment the animals, freely moving in their cages, were submitted to 2DG administration (50 mg/100 g body wt) via atrial catheter infusion. After 2DG infusion, the plasma prolactin of vehicle-treated (VEH) rats increased rapidly, reaching a peak at 10 min (34.3 ± 7.6 ng/ml; P<0.01). In contrast, 2DG infusion failed to induce any significant change in the plasma prolactin levels of bromocriptine-treated (BR) rats. BR rats showed higher resting glucose levels than control rats (8.2 ± 0.28 mM (BR) vs 6.0 ± 0.18 mM (VEH); P<0.01). However, the hyperglycemic response of BR rats to 2DG injection was 30% lower than that of VEH rats (P<0.05). BR rats also showed a rapid rise in plasma insulin levels reaching a peak at 30 min after 2DG injection (243% higher than basal values; P<0.01). This increased rise in the insulin response to neurocytoglucopenia of BR rats was blocked by previous intravenous injection of atropine methyl nitrate (0.2 mg/100 g body wt). The present results suggest that chronic treatment with bromocriptine determines a strong increase in the parasympathetic tone response to neurocytoglucopenia, which is responsible for the higher stimulation of insulin secretion observed in BR rats. The data also provide further evidence that D2-dopaminergic agonist can block neurocytoglucopenia-induced prolactin release.