Hormonal Sensitivity of Adenylyl Cyclase in the Myocardium, Brain and Testes of 18-month-old Non-Diabetic and Diabetic Rats

The alterations and abnormalities in hormone-sensitive adenylyl cyclase (AC) system occur at early stages of the type 2 diabetes mellitus (T2DM) and at later stages of the disease they are, according to our view, one of the factors causing T2DM complications. To study the changes in AC system likely to be involved in the development of these complications one needs a very long model of T2DM.

Purpose: The aim of this work was the study of AC system in the myocardium, brain and testes of three-, eight- and 18-month-old male rats with experimental T2DM compared with control animals of the same age.

Methodology: Neonatal model of T2DM was induced by the treatment of five-day pups with streptozotocin (80 mg/kg), at the age of three months streptozotocin-treated rats had glucose tolerance. The determination of the basal AC activity and its regulation by hormones was carried out in the plasma membranes from the tissues of diabetic and control rats, using [a-32P]-ATP as substrate.

Results: With increasing age, three to 18 months, in the myocardium and testes of diabetic and control rats the AC stimulating effects of b-agonists and relaxin (myocardium), and gonadotropin and PACAP-38 (testes) decreased, in diabetic rats to a much greater extent. In the brain the influence of age on AC stimulation by hormones was less pronounced, and only AC effect of PACAP-38 drastically decreased in 18-month-old diabetic and control rats. AC inhibitory effects of somatostatin (all investigated tissues), 5-nonyloxytryptamine (brain) and noradrenaline (myocardium) reduced in eight- and 18-month-old diabetic rats, indicating the weakening of AC inhibiting pathways in a rat model of T2DM.

Conclusion: The hormonal regulation of AC system in the brain, myocardium and testes of 18-month-old control and diabetic rats significantly weakened, and in very long T2DM these abnormalities induced by the combined influence of DM and aging are expressed to a large extent.