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 childhood 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 (1 ½M-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 1 ½-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 1 ½M-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 1 ½M-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 G(s)-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 1 ½M-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 PACAP-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.

Functional activity of hormanal signaling systems and their sensitivity to regulatory actions of hormones in diabetes mellitus (DM) and its complications are altered. The activity of receptor forms of guanylyl cyclases (rGC) sensitive to natriuretic peptides, ANP and CNP, in tissues of female rats with 240-days neonatal streptozotocin DM and the influence of intranasal administration of insulin and serotonin (6 weeks, daily dose is 0.48 IU of insulin or 20 microg of serotonin to rat) on this activity were studied. In diabetic animals, the increase of the basal activity of rGC in the myocardium and its decrease in the uterus and ovaries were found, whereas the brain showed no differences from control animals. The treatment of diabetic rats with insulin led to a decrease in the basal activity of rGC in the myocardium and to its restoration to normal level in the ovaries. Serotonin treatment induced a less pronounced compared with insulin decrease in the basal activity of the enzyme in the myocardium and also a slight increase the activity in the brain. In the myocardium of diabetic rats, the weakening of GC stimulating effect of ANP and, on the contrary, the strengthening of CNP effect were observed. In the ovaries, GC stimulating effect of CNP and, to a lesser degree, the corresponding effect of ANP were decreased. In the uterus and the brain, the sensitivity of rGC to hormones was practically not changed. The administration of insulin to diabetic rats induced an increase in GC effect of ANP in the myocardium to its values in control animals and a decrease in CNP effect as well as in partially restored GC effect of CNP in the ovaries. Serotonin treatment led to some increase in the effects of natriuretic peptides in the brain of both control and diabetic animals. Summing up, in neonatal model of type 2 DM in the myocardium and the tissues of reproductive system of rats the functioning of natriuretic peptide-sensitive rGC is altered in the myocardium and the tissues of reproductive system of model rats with neonatal type 2 DM. Treatment of animals with insulin substantially restores rGC activity while intranasal administration of serotonin has little effect.