Alterations of Hormone-Sensitive Adenylyl Cyclase System in the Tissues of Rats with Long-Term Streptozotocin Diabetes and the Influence of Intranasal Insulin
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 of -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. 1. Introduction The type 1 diabetes mellitus (T1DM), one of the most severe metabolic disorders in humans, characterized by hyperglycemia due to a relative or an absolute lack of insulin, leads to many complications, such as coronary heart diseases, hypertension, atherosclerosis, neurodegenerative diseases, cognitive deficit, and dysfunctions of the reproductive system [1, 2]. One of the causes of these complications is the alterations in hormone-sensitive signaling systems, the adenylyl cyclase (AC) system in particular [3, 4]. It was shown that changes in the functional activity of AC system in the heart, brain, and reproductive tissues in experimental T1DM were tissue and hormone specific [5–10]. Generally, the effects of hormones acting on AC via G proteins of the inhibitory type ( ) were changed to a greater degree compared with those realized via G proteins of the stimulating type ( ), likely due to a decrease of proteins expression and a reduction of their functional activity and coupling with upstream and downstream signal proteins. The degree of alterations and abnormalities in hormonal signaling systems is well correlated with the severity of T1DM and its complications [11, 12]. As a result, at the later stages of the disease characterized by pronounced clinical symptoms,
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