Alterations of Hormone-Sensitive Adenylyl Cyclase System in the Tissues of Rats with Long-Term Streptozotocin Diabetes and the Influence of Intranasal Insulin

Abstract

One of the causes of complications in type 1 diabetes mellitus (T1DM) is the changes in adenylyl cyclase (AC) signaling system, identified on the early stages of the disease. However, the most significant disturbances in this system occur on the later stages of T1DM, which ultimately leads to severe complications, but functional state of the AC system in late T1DM is poorly understood. The aim of this work was to study alterations in AC system sensitive to biogenic amines and polypeptide hormones in the heart, brain, and testes of male rats with long-term, 7-month, streptozotocin T1DM and to assess the influence on them of 135-day therapy with intranasal insulin. It was shown that AC effects ofβ-adrenergic agonists in the heart, serotonin receptor agonists and PACAP-38 in the brain, chorionic gonadotropin and PACAP-38 in the testes, and somatostatin in all investigated tissues in long-term T1DM were drastically decreased. The treatment with intranasal insulin (0.48 IU/day) significantly restored these effects. The results were obtained suggesting that long-term T1DM induces significant alterations in hormone-sensitive AC system in the heart, brain, and testes that are much more pronounced, compared with short-term T1DM, and include a large number of hormonal regulations.