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 D 2 -dopaminergic agonist, on hyperglycemia and insulin secretion in response to neurocytoglucopenia induced by 2-deoxy--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 D 2 -dopaminergic agonist can block neurocytoglucopenia-induced prolactin release.

Angiotensin-converting enzyme inhibition changes the metabolic response to neuroglucopenic stress

“…34 Similar data have been described with chronic bromocriptine treatment increasing parasympathetic response to neuroglucopenic stress. 8 In the present study, it has also been observed that plasma triglyceride neuroglucopenic stress response was significantly modified by the chronic enalapril treatment. In enalapril-treated rats, an increase in triglyceride levels was observed after 2DG infusion while the controls showed no alteration of plasma triglyceride levels.…”

“…Neuroglucopenic stress was induced by infusion of 50 mg/100 g of 2-deoxy-D-glucose 10% solution. 8 The animals were divided into three experimental groups: control rats submitted to neuroglucopenic stress (VD), enalapriltreated rats subjected to neuroglucopenic stress (ED), and enalapril-treated rats receiving NaCl 0.9% infusion instead of 2DG solution (ES).…”

Bromocriptine, a Dopamine (D 2 ) Receptor Agonist, Used Alone and in Combination with Glipizide in Sub–Therapeutic Doses to Ameliorate Hyperglycaemia

“…p.o. [8]. Group 4 (Sub therapeutic): treated with the sub therapeutic doses of both test (bromocriptine in a dose of 2 mg/kg body wt) and standard (glipizide in a dose of 1.25mg/kg body wt) drugs p.o.…”

The potential role of D2 dopamine receptors as a target in the management of neuroendocrine tumors

“…1,2 The D 2 receptors have been involved in adrenal regulation and response to stressful stimuli, in addition to their classical role in prolactin-secreting adenomas. [8][9][10][11][12][13][14][15] Indeed, the dopaminergic agents have been the mainstay in the treatment of prolactinomas, through an action on the D 2 receptors. 16 Furthermore, somatotroph pituitary tumors occasionally show dramatic anti-secretory and anti-proliferative responses to dopaminergic agents.…”