Abstract
Cardiovascular diseases and dysfunctions of the reproductive system are common complications of type 2 diabetes (T2D), and, therefore, development of new approaches for the alleviation of these pathologies is highly important. Bromocriptine (BC), an agonist of type 2 dopamine receptors, recently became widely used for the treatment of type 2 diabetes; this drug both restores energy metabolism and prevents the development of cardiovascular disease. However, the targets of BC and mechanisms underlying its action are still poorly characterized. The aim of the present work was to investigate the effect of BC treatment on the functional activity of the adenylyl cyclase signaling system (ACSS) in the myocardium and testes of male rats suffering from type 2 diabetes induced by high-fat diet and administration of streptozotocin (25 mg/kg). Oral BC administration (0.6 mg/kg every other day for 60 days) started 90 days after the commencement of highfat diet. Body weight and triglyceride levels were elevated in diabetic rats. Glucose tolerance of the animals was impaired, and they developed insulin resistance. BC treatment enabled the recovery of glucose metabolism parameters and increased the sensitivity of tissues to insulin. Adenylyl cyclase (AC) stimulation by guanylyl imidodiphosphate (GppNHp), relaxin, and the β-adrenergic receptor (β-AR) agonists isoproterenol and norepinephrine in the myocardium of diabetic rats was impaired, while the stimulatory effects of the β3-agonists BRL-37344 and CL-316243 persisted. The inhibitory effect of somatostatin on forskolin-stimulated AC activity was attenuated, while the inhibitory effect of norepinephrine mediated by α2-AR was enhanced. BC treatment normalized adrenergic signaling in the myocardium and partially restored the effects of relaxin and somatostatin on AC. AC activity, both basal and stimulated by GppNHp, forskolin, human chorionic gonadotropin, and pituitary AC-activating polypeptide, decreased in the testis of diabetic rats, and the inhibitory effect of somatostatin was attenuated. BC treatment induced only slight changes in the testicular ACSS. Thus, prolonged BC treatment restored the functional activity of ACSS in the myocardium and testes of diabetic rats; this accounts for the therapeutic effect of BC on the impaired functioning of the cardiovascular and reproductive systems in T2D and should be taken into account upon the selection of treatment strategies for T2D and its complications.
Published Version
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