Abramova T. Remodeling of the Endocrine Apparatus of the Pancreas in Normotensive and Hypertensive Rats with Experimental Diabetes Mellitus.

The dissertation presents a theoretical justification and an experimental solution to an actual scientific task, which is to establish mechanisms for the remodeling of the endocrine apparatus of pancreatic islets in normotensive Wistar rats and spontaneously hypertensive SHR rats. Also, the parameters of the reactivity of endocrinocytes in the course of experimental diabetes mellitus were studied. The studies were performed on adult male SHR rats with systolic blood pressure at the time of the experiment 155.7 ± 0.9 mm Hg and fasting glycemia level 4.73 ± 0.10 mmol/L. The control group of animals was represented by adult male Wistar rats with systolic blood pressure at the time of the experiment 105.0 ± 1.1 mm Hg and fasting blood glucose level 3.94 ± 0.09 mmol/L. The insulin concentration in the blood of SHR rats was 27 % higher than that of Wistar rats, and was 10.99 ± 0.37 μIU/ml. Moreover, the HOMA index in hypertensive rats reached 3.41 ± 0.21 vs 1.43 ± 0.08 in Wistar rats. The sequential immunofluorescence staining of the serial sections of the pancreas with the detection of insulin, glucagon and somatostatin in endocrinocytes was a specific feature of the methodological approach to the study of pancreatic endocrine apparatus structure. This approach made it possible to carry out pancreatic reconstruction, to classify and describe pancreatic islets of various types, to establish quantitative parameters of endocrinocytes various types distribution in the islets, their population density in the pancreas, and to obtain data on specific contents of insulin, glucagon and somatostatin in pancreatic islets and in the pancreas in the whole. Based on a quantitative immunofluorescence study, it was shown that fasting SHR rats are characterized by fasting normoglycemia. Meanwhile, a change in the glycemic profile of a diabetic type was detected during the glucose tolerance test. The formation of arterial hypertension in SHR rats is accompanied by remodeling of the insular apparatus of the pancreas: the number of pancreatic islets is reduced by 2 times, the number of beta cells is reduced by 8 times, withal pancreatic islets with a cross-sectional area of less than 1500 μm2 prevail. Despite moderate hypertrophy of beta-endocrinocytes and an increase in insulin concentration in them, the insulin content in the pancreas in hypertensive animals is about 3 times less in comparison with normotensive Wistar rats. It was found that the pancreatic islets of hypertensive SHR rats are characterized by a 2-fold increase in the number of alpha-endocrinocytes and glucagon content in the pancreas compared to normotensive Wistar rats. At the same time, the number of delta-endocrinocytes is 18 % higher than the corresponding indicator of normotensive Wistar rats, however, the specific somatostatin content is only 73 % of the value of this indicator in Wistar rats. It was shown that in the endocrinocytes of pancreatic islets of hypertensive SHR rats, the area of immunoreactive to the anti-apoptotic protein Bcl2 material is reduced by 2 times, and its relative content in pancreatic islets becomes 3 times lower than in normotensive Wistar rats. Meanwhile, there were no significant differences between normotensive and hypertensive rats in the expression values of the proapoptotic p53 protein in endocrinocytes.