[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].
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 (β3-AR)--isoproterenol and norepinephrine were decreased in the miocardium of the diabetic rats. The corresponding effects of the β-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.
K V
KV
Derkach
V M
VM
Bondareva
I V
IV
Moyseyuk
A O
AO
Shpakov
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000284:Administration, Oral; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001971:Bromocriptine / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000473:pathology; D059305:Diet, High-Fat / Q000009:adverse effects; D004149:Dioxoles / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology*; D004334:Drug Administration Schedule; D004983:Ethanolamines / Q000494:pharmacology; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D006801:Humans; D007333:Insulin Resistance; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012065:Relaxin / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects*; D013311:Streptozocin; D013737:Testis / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; D004149:Dioxoles; D018491:Dopamine Agonists; D004983:Ethanolamines; D014280:Triglycerides; C076126:disodium (R,R)-5-(2-((2-(3-chlorophenyl)-2-hydroxyethyl)-amino)propyl)-1,3-benzodioxole-2,3-dicarboxylate; D006165:Guanylyl Imidodiphosphate; D001971:Bromocriptine; C057368:BRL 37344; D013311:Streptozocin; D012065:Relaxin; D000262:Adenylyl Cyclases; D007545:Isoproterenol; D009638:Norepinephrine