Dynamics of c-kit immunopositive pancreatic beta cells influenced by exogenous factors or endogenous pathology
Authors: Ivanenko T. V. , Kolesnyk Yu. M. , Abramov A. V. 
Published: June 2024

Mechanisms of beta-endocrinocyte differentiation involving c-kit may be associated with a number of processes, including signaling pathways and regulatory mechanisms. Such factors as activation of the c-kit signaling pathway, an increase or decrease in cell proliferation and survival, regulation of differentiation gene programs and stem cells are important in controlling self-preservation and regulating the cellular number and types, that are differentiated being impacted by intermittent hypoxic hypoxia, hypertension and diabetes mellitus.
The aim of the work is to determine the dynamics of c-kit proliferative factor in beta cells under an exogenous influence (intermittent hypoxic hypoxia) and endogenous pathology (arterial hypertension and diabetes mellitus).
Materials and methods. The study was conducted using 15 white Wistar rats and 5 spontaneously hypertensive rats (SHR), which were divided into 4 groups of 5 animals each. Group 1 – control (intact) rats, group 2 – animals with experimental diabetes mellitus, group 3 – rats with hereditary arterial hypertension (SHR), group 4 – animals exposed to the effect of intermittent hypoxic hypoxia. At the end of the experiment, the animals were euthanized, organs were harvested and processed, serial histological pancreatic sections 5 µm thick were deparaffinized and retrieved. Insulin and c-kit+ beta progenitor cells were detected by the immunofluorescence method using antibodies. Immunofluorescent reactions were studied using an AxioImager-M2 fluorescence microscope.
Results. The quantitative indicator of beta cells was almost 6 times decreased in rats with diabetes mellitus. Concentrations of insulin in animals of this group were increased compared to intact animals and the marker of proliferative activity was decreased without changes in the percentage of c-kit-immunopositive beta cells. The course of hereditary arterial hypertension in SHR was accompanied by an 8-fold decrease in the number of beta cells per 1 cm2, an increase in insulin in beta cells as compared to the animals of both intact and experimental diabetes groups. Regarding the c-kit expression in beta cells, it was significantly reduced only in the group of intact animals and the number of c-kit-immunopositive beta cells was almost 2.8 times decreased.
In the experimental group of animals exposed to hypoxic hypoxia, the number of beta cells per measurement unit was significantly increased, the concentration of insulin in beta cells was increased as compared to the intact animals, but lower than that in rats with diabetes and hypertension. The marker of proliferative activity c-kit was decreased compared to both intact and diabetic animals. As for the number of c-kit-immunopositive beta cells, it did not differ statistically from that in intact and diabetic animals, but was higher than that in SHR.
Conclusions. The development of experimental diabetes in Wistar rats and hereditary hypertension in SHR results in a significant decrease in the specific density of beta cells in the pancreas in contrast to the effect of multiple-day hypoxic training, which stimulates an increase in the density of insulin-synthesizing endocrinocytes. Experimental conditions, diabetes mellitus, hypertension and adaptation to hypoxia, are accompanied by an increase in insulin and a decrease in the c-kit expression in beta cells. However, the number of c-kit-immunopositive beta cells in the pancreatic islets significantly decreases only with the development of hereditary arterial hypertension.