Features of beta cell differentiation during the development of type 2 diabetes mellitus
https://doi.org/10.15789/1563-0625-FOB-16880
Abstract
Type 2 diabetes mellitus is characterized by a mild inflammatory reaction in the pancreas, which affects the structure and function of the pancreatic islets: the number of β-cells decreases and the number of α-cells increases. The work examined the features of β-cell differentiation in the development of experimental type 2 diabetes mellitus and while reducing the inflammatory process. Biochemical, histological methods, enzyme-linked immunosorbent assay, immunohistochemical methods were used using primary antibodies to insulin, glucagon, proliferation marker Ki-67 and secondary antibodies labeled with fluorescent dyes. Streptozotocin and nicotinamide were used to model type 2 diabetes mellitus, and the sodium salt of 5-amino-2,3-dihydrophthalazine-1,4-dione was used to reduce the inflammatory response. Previous studies have shown that it changes the macrophage phenotype from proinflammatory M1 to anti-inflammatory M2. In type 2 diabetes mellitus, against the background of a decrease in the number of macrophages with the CD163 marker and the concentration of the cytokine TGF-β1, which have an anti-inflammatory effect, in the pancreatic islets, a decrease in the number of β-cells and their functional activity was observed, while the content of α-cells synthesizing glucagon increased. After administration of the sodium salt of 5-amino-2,3-dihydrophthalazine-1,4-dione, the opposite picture was observed in the pancreatic islets: against the background of an increase in the number of CD163+ macrophages and the content of TGF-β1, the number of β cells increased and the number of α cells decreased-cells. The increase in the number of insulin-synthesizing cells was not accompanied by their mitotic activity. It is likely that a decrease in the number of CD163+ macrophages and the level of the antiinflammatory cytokine TGF-β1 in the islets are factors contributing to changes in the cell microenvironment and, as a consequence, the differentiation of β-cells into α-cells. On the contrary, an increase in the number of CD163+ macrophages and TGF-β1 against the background of administration of the sodium salt of 5-amino-2,3-dihydrophthalazine-1,4-dione presumably promotes reverse differentiation of α-cells into β-cells and restoration of insulin synthesis pancreas. Targeted effects on the microenvironment of cells in the pancreatic islet in type 2 diabetes mellitus may be a new approach to treating the disease.
About the Authors
A. V. BelousovaRussian Federation
Anna V. Belousova - Research Associate, Laboratory of Morphology and Biochemistry, Institute of Immunology and Physiology, Ural Branch, Russian Academy of Sciences.
106 Pervomajskaya St Yekaterinburg 620049
Phone: +7 (906) 806-55-09
Competing Interests:
None
K. V. Sokolova
Russian Federation
Senior Research Associate, Laboratory of Morphology and Biochemistry, Institute of Immunology and Physiology, Ural Branch, Russian Academy of Sciences.
Yekaterinburg
Competing Interests:
None
I. G. Danilova
Russian Federation
PhD, MD (Biology), Professor, Head, Laboratory of morphology and biochemistry, Institute of Immunology and Physiology, Ural Branch, Russian Academy of Sciences.
Yekaterinburg
Competing Interests:
None
M. V. Chereshneva
Russian Federation
PhD, MD (Medicine), Professor, Chief Research Associate, Laboratory of Immunophysiology and Immunopharmacology, Institute of Immunology and Physiology, Ural Branch, Russian Academy of Sciences.
Yekaterinburg
Competing Interests:
None
V. A. Chereshnev
Russian Federation
PhD, MD (Medicine), Professor, Full Member, Russian Academy of Sciences, Chief Research Associate, Laboratory of Immunophysiology and Immunopharmacology, Institute of Immunology and Physiology, Ural Branch, Russian Academy of Sciences.
Yekaterinburg
Competing Interests:
None
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Review
For citations:
Belousova A.V., Sokolova K.V., Danilova I.G., Chereshneva M.V., Chereshnev V.A. Features of beta cell differentiation during the development of type 2 diabetes mellitus. Medical Immunology (Russia). 2024;26(5):1037-1044. (In Russ.) https://doi.org/10.15789/1563-0625-FOB-16880