THE INFLUENCE OF LONG-TERM DIABETES MELLITUS INDUCED BY STREPTOZOTOCIN TREATMENT OF SIX-WEEK RATS ON THE FUNCTIONAL
ACTIVITY OF ADENYLYL CYCLASE SYSTEM
A.O. Shpakov, K.V. Derkach, O.V. Chistyakova, I.V. Moyseyuk, V.M. Bondareva
I.M. Sechenov Institute of Evolutionary Physiology and Biochemistry RAS, St. Petersburg;
e-mail: alex_shpakov@list.ru
The alterations occurring in diabetes mellitus (DM) of the type 1 in the adenylyl cyclase signaling system (ACSS) are one of the key causes of complications of the disease. As type
1 DM most often diagnosed in child-hood and adolescence, the actual problem is the study of alterations in ACSS in the early development of the disease. For this we developed a
prolonged model of type 1 DM, which was induced by treatment of six-week-old rats with moderate doses of streptozotocin (1½M-DM), and studied the functional state of ACSS
in the brain, myocardium, and testes of rats with this model of the disease, seven months after its initiation. Model 1½-DM was compared with the seven-month model of type 1
DM, which was induced by streptozotocin treatment of adults, five-month-old, animals (5M-DM). It is shown that in 1½M-DM in the tissues of diabetic rats the functional activity
of ACSS sensitive to biogenic amines and polypeptide hormones was significantly changed. In rats with 1½M-DM the adenylyl cyclase (AC) inhibiting effects of somatostatin
(in all studied tissues), norepinephrine (in the myocardium and brain), and agonists of type 1 serotonin receptor (in the brain) were weakened the most. In the brain also decreased AC
stimulating effects of relaxin, isoproterenol and agonists of Gs-protein-coupled serotonin receptors, in the myocardium - corresponding effects of GppNHp, relaxin and
β-adrenergic agonists, and in the testes - AC effects of GppNHp and chorionic gonadotropin. When comparing the models 1½M-DM and 5M-DM, the most pronounced
differences between them were found in the influence of DM on hormonal regulation of ACSS in the brain, and this refers both to AC stimulating effects of dopamine and PA-CAP-38,
and to AC inhibiting effects of bromocryptine and somatostatin. These results indicate significant alterations in the hormonal regulation of the nervous, cardiovascular and reproductive
systems in rats with early induction of type 1 DM, in some cases more severe compared with late model of 5M-DM. These alterations can be the basis for the development of diabetic
cardiomyopathy, cognitive deficits and hypogonadotropic states, which are often detected in children and adolescents with type 1 DM.
Key words: adenylyl cyclase, adrenergic receptor, gonadotropin, brain, myocardium, diabetes mellitus, testes, serotonin, somatostatin
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