The functional state of the
adenylyl cyclase signaling system (ACSS) and its regulation by
hormones, the inhibitors of
adenylyl cyclase (AC)--
somatostatin (SST) in the brain and myocardium and
5-nonyloxytryptamine (5-NOT) in the brain of rats of different ages (5- and 7-month-old) with experimental
obesity and a combination of
obesity and
type 2 diabetes mellitus (DM2), and the effect of long-term treatment of animals with intranasally administered
insulin (II) on ACSS were studied. It was shown that the basal AC activity in rats with
obesity and DM2 was increased in the myocardium, and to the lesser extent in the brain, the treatment with II reducing this parameter. The AC stimulating effects of
forskolin are decreased in the myocardium, but not in the brain, of rats with
obesity and DM2. The treatment with II restored the AC action of
forskolin in the 7-month-old animals, but has little effect on it in the 5-month-old rats. In
obesity the basal AC activity and its stimulation by
forskolin varied insignificantly and weakly changed in treatment of animals with II. The AC inhibitory effects of SST and 5-NOT in the investigated pathology are essentially attenuated, the effect of SST to the greatest extent, which we believe to be associated with a reduction in the functional activity of Gi-
proteins. The II treatment of animals with
obesity and with a combination of
obesity and DM2 restored completely or partially the AC inhibiting effects of
hormones, to the greatest extent in the brain. Since impaired functioning of ACSS is one of the causes of the
metabolic syndrome and DM2, their elimination by treatments with II can be an effective approach to treat these diseases and their CNS and cardiovascular system complications.