HORMONAL REGULATION OF ADENYLYL CYCLASE IN THE MYOCARDIUM OF MALE RATS WITH METABOLIC SYNDROME AND THE INFLUENCE OF TREATMENT WITH METFORMIN AND INTRANASALLY ADMINISTERED INSULIN

Background. Metabolic syndrome (MS) is closely associated with the development of diseases of the cardiovascular system, one of the causes of which are changes in the hormonal system, including adenylyl cyclase signaling system (ACSS), which is sensitive to agonists of adrenergic receptors (AR) and the other hormones and plays a key role in the regulation of myocardial function. However, the functional state of the myocardial ACSS in MS is currently poorly understood. Objective. The aim of the work was to study the hormone sensitivity of ACSS in the myocardium of rats with MS and the influence of metformin (MF) and intranasally administered insulin (I-I) treatment on it. Design and methods. The MS in rats was caused by two-month consumption of 30% sucrose solution and diet enriched by saturated fat. The treatment of the MS-rats with MF (200 mg/kg/day) and I-I (0.5 IU/rat/day) was performed for 5 weeks. Results. The MF and I-I treatment of MS-rats led to restoration of glucose tolerance, insulin sensitivity and lipid metabolism. In the myocardium of MS-rats the adenylyl cyclase (AC) stimulating effects of ß1/ß2-AR agonists, relaxin and glucagon-like peptide-1 were decreased, the relationship between ß1/ß2- and ß3-AR was shifted to ß3-AR, and the inhibitory effect of 2-chloro-N⁶-cyclopentyl adenosine, an agonist of A₁-adenosine receptors, was reduced. The treatment with MF and, to a lesser extent, with I-I restored the hormonal regulation of AC in the myocardium. Conclusion. Thus, in the myocardium of MS-rats the hormonal sensitivity of ACSS was impaired, and the MF and I-I treatment led to its complete or partial restoration, which is one of the mechanisms of cardioprotective effect of these drugs.

метаболический синдром, миокард, аденилатциклаза, адренергический рецептор, метформин, metabolic syndrome, myocardium, adenylyl cyclase, adrenergic receptor, metformin

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