Tkachuk Y. Morpho-functional changes of pituitary-adrenal system in experimental diabetes mellitus and its management

The investigation involved 124 mature white male Wistar rats (average weight for male: 180-200 grams), which were divided into three groups. Group I included 10 intact animals, which underwent no manipulations. Group II was divided into 2 subgroups: 2а - control (30 animals), 2b (42 animals) with simulated experimental streptozotocin-induced diabetes mellitus (ESDM). Group III involved animals (42 rats) with simulated ESDM who received antidiabetic therapy starting from the 14th day of experiment: 3а subgroup (14 rats) animals were administered exenatide injections, 3b subgroup (14 animals) – insulin glargine injections, 3c subgroup (14 animals) – complex therapy: subcutaneous injections of insulin glargine in the morning and exenatide injections in the evening. Blood glucose levels increased considerably by 1.8 times (р<0.01), HbA1c – by 1.9 times (р<0.01) on the 7th day of experiment, after the injection of a single dose of streptozotocin. The nucleocytoplasmic index (NCI) in corticotropic endocrinocytes increases. On the ultrastructural level the volume density of marginated secretory granules (SG) also increases. Significant thickening of zona fasciculata by 23.95% (р=0.0007) is noticed in adrenal cortex. The endocrinocytes’ profile area is significantly decreased in zona fasciculata that associated with the decrease of lipid droplets (LD) by 48.85% in their cytoplasm. The cortisol level increases by 1.46 times (р=0.0074). Linear proportional associations are revealed between the glucose and cortisol levels r=+0.82 (р=0.0244). Functional activity of pituitary-adrenal system increases in the setting of constantly progressing hyperglycemia at early stages of ESDM development (14-28 days). The number of corticotropic endocrinocytes per 0.01 mm2 of adenohypophysis increases by 1.59-2.03 times, profile area of their nuclei is also statistically significantly increased leading to the increase of NCI, and the volume density of SG increases by 1.8 times. Levels of adrenocorticotropic hormone (ACTH) increase by 2-4 times as compared to the control indices. Morpho-functional changes in adrenal cortex are evident in: thickening of all its zones; increase of endocrinocytes’ profile area of all zones and their nuclei; increase of volume density of lipid granules in endocrinocytes. Blood cortisol level also increases to 18.27±2.21 ng/ml on the 14th day of experiment and to 23.42±2.86 ng/ml on the 28th day (р<0.01 in all cases), as compared to the control indices. The number of corticotrophs per 0.01 mm2 of adenohypophysis area decreases starting from the 56th day of experiment. Most of the endocrinocytes undergo irreversible changes on the light-optical and ultrastructural levels, like hydropic degeneration and colliquative necrosis. ACTH level decreases as compared to the previous term of experiment. On the 70th day of experiment chronic overwork of adrenal system leads to adrenal fatigue. Morphologically these changes are characterized by: hydropic degeneration of endocrinocytes of all zones; partial necrosis of some fasciculata cells; decrease of volume density of lipid droplets in endocrinocytes of all zones; decrease of blood cortisol level to control indices. Changes in endocrinocytes of adrenal cortex on the 56th -70th day of ESDM course are associated with circulatory and hemic hypoxia as a result of diabetic microangiopathy development. The latter is characterized by the: increase of the area of capillaries and their walls; increase in Vogenvort index; destructive changes in endotheliocytes and myocytes, marked hemoreologic disorders. Consequently, it became possible to emphasize three main stages in the dynamics of morphofunctional changes of pituitary-adrenal system of rats with ESDM: reactive changes (day 7), compensatory processes (day 14-42), fatigue and destructive changes (day 42-56). The use of exenatide and insulin glargine as a monotherapy in ESDM is effective only at early stages of experiment. The findings of our investigation show that complex use of insulin glargine and exenatide is the best option for the treatment of diabetic endocrinopathy, as it provides normalization of glucose profile in diabetic animals. This complex therapy results in: cellular and intracellular regeneration of endocrinocytes in the pituitary gland and adrenal cortex; reactivation of quantitative and qualitative parameters of structural components of microcirculatory blood flow in adrenal cortex. Branch - medicine.