THE INFLUENCE OF TWO-MONTH TREATMENT WITH BROMOCRYPTINE
ON ACTIVITY OF THE ADENYLYL CYCLASE SIGNALING SYSTEM
IN THE MYOCARDIUM AND TESTES OF RATS WITH TYPE 2 DIABETES MELLITUS
K.V. Derkach, V.M. Bondareva, I.V. Moyseyuk, A.O. Shpakov 1
I.M. Sechenov Institute of Evolutionary Physiology and Biochemistry RAS, St. Petersburg;
1 e-mail: alex_shpakov@list.ru
One of the common complications of type 2 diabetes mellitus (DM2) are cardiovascular diseases and dysfunctions
of the reproductive system, indicating the urgency of developing new approaches to their correction.
Last years for the treatment of DM2 began to use bromocryptine (BC), the agonist of type 2 dopamine receptors,
which not only restores the energy metabolism, but also prevents the development of cardiovascular diseases.
However, the mechanisms and targets of BC action are poorly understood. The purpose of this study was to
investigate the effect of BC treatment on functional activity of adenylyl cyclase signaling system (ACSS) in the
myocardium and testes of male rats with DM2, which is caused by high-fat diet and treatment with streptozotocin
(25 mg/kg). The treatment with BC (60 days, orally at a dose of 0.6 mg/kg once every two days) was started
90 days after the beginning of high-fat diet. Diabetic rats had an increased body weight, elevated triglycerides
level, impaired glucose tolerance, and insulin resistance. The treatment with BC resulted in the restoration of
glycometabolic indicators and in the improvement of insulin sensitivity. Adenylyl cyclase (AC) stimulating effects
of guanylylimidodiphosphate (GppNHp), relaxin, and agonists of β-adrenergic receptors (β-AR) — isoproterenol
and norepinephrine were decreased in the miocardium of the diabetic rats. The corresponding effects
of theβ3-agonists BRL-37344 and CL-316243 was preserved. The inhibitory effect of somatostatin on forskolin-
stimulated AC activity was attenuated, while the inhibitory effect of noradrenaline mediated through α2-AR
increased. The treatment with BC resulted in the normalization of the adrenergic signaling in the myocardium
and partially restoration of AC effects of relaxin and somatostatin. In the testes of diabetic rats, the basal and
stimulated by GppNHp, forskolin, human chorionic gonadotropin and pituitary AC-activating polypeptide AC
activity were decreased, and the inhibitory effect of somatostatin was attenuated. The changes in testicular
ACSS in the case of BC treatment were weakly expressed. Thus, long-term BC treatment restores the functional
activity of ACSS in the myocardium and testes of diabetic rats that underlies the therapeutic effect of BC on
functions of the cardiovascular and reproductive systems disturbed in DM2 and should be considered when developing
strategies for treatment type 2 diabetes and its complications.
Key words: adrenergic agonist, adenylyl cyclase, bromocryptine, gonadotropin, dyslipidemia, insulin
resistance, myocardium, norepinephrine, testes, somatostatin, glucose tolerance
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