Beta-adrenergic regulation of adenylyl cyclase signaling system in the myocardium and brain of rats with obesity and type 2 diabetes mellitus as affected by long-term intranasal insulin administration

The stimulatory effects of norepinephrine, isoproterenol and selective ß3-adrenoceptor agonists BRL 37344 and CL 316.243 on the adenylyl cyclase signaling system (ACSS) in the brain and myocardium of young and mature rats with experimental obesity and type 2 diabetes mellitus (DM2) (disease induction at 2 and 4 months of age, respectively) and the influence of the long-term intranasal insulin (I-I) administration were studied. It was shown that the AC-stimulatory effects of ß-agonist isoproterenol in animals with obesity and DM2 practically did not change. The respective effects of norepinephrine on the AC activity slackened in the brain of young and mature rats and myocardium of mature rats, while the I-I treatment led to their partial recovery. In the brain and myocardium of mature rats with obesity and DM2 an increase in the AC-stimulatory effects of ß3- AR agonists was observed, while in young rats the similar influence of the same pathologies was mißsing. The I-I treatment resulted in an attenuation of the AC-stimulatory effects of ß3-agonists to their control level. Since the disruption of the adrenergic agonist-sensitive ACSS is one of the causes of metabolic syndrome and DM2, the recovery of ACSS dysfunctions by the long-term I-I administration offers one of the ways of correcting these diseases and their complications in the nervous and cardiovascular systems.