Putilin D. Mechanisms of the changes in the functional state of the pancreatic lymph nodes’ cells and the parapancreatic adipose tissue in the experimental diabetes mellitus and after the metformin’s introduction.

The thesis is devoted to the clarification of the peculiarities of the changes in the functional state of the lymphocytes of the pancreatic lymph nodes and parapancreatic adipose tissue in the experimental diabetes mellitus and after the metformin’s introduction. To achieve the goal, immunofluorescence, immunohistochemical, methods of molecular genetic analysis (RT-PCR), computer analysis of images, statistical methods were used. As a result of the work, a complex of key pathophysiological and functional changes in PLN and PAT cells was found in the ESIDM conditions: changes in the lymphocyte immune metabolism; violation of the formation of peripheral immunological tolerance; PRR activation of the congenital immune system on the lymphocytes of PLN and PAT adipocytes; changes in the distribution of effector T cells in the PLN; increase of pro-inflammatory signaling in the PAT on the background of the mRNA Foxp3 level’s reduction. The scientific concepts are extended due to the role of adipose tissue in the progression of diabetes. It has been determined that in the ESIDM conditions the number of TLR2+ and TLR4+ -adipocytes in parapancreatic fiber increases, which induces proinflammatory signaling in the adipose tissue and increases the mRNA expression of IL1β and IL17A on the background of the transcriptional Foxp3 repression. The expediency of the metformin’s use for the correction of immune disorders developing in the DM is substantiated. For the first time, the metformin’s ability has been shown to influence on the transcriptional activity of the AMPK1α and mTOR genes, to reduce the number of lymphocytes expressing PRR, to alter the distribution of Treg and Th17 cells in the PLN of the diabetic rats.