Peculiarities of distribution of patterns with high and low expression of c-Kit protein in the pancreas of rats with experimental diabetes

Abstract

The c-Kit protein, also known as CD117, is a membrane receptor tyrosine kinase, and plays an important role in various cellular processes including cell proliferation, survival and differentiation. In particular, at the embryonic stage of pancreatogenesis, c-Kit protein participates in the process of beta-cell differentiation from pancreatic progenitor cells, and controls the subsequent migration and invasion of endocrinocytes with the formation of new pancreatic islets. Activation of c-Kit-mediated receptor mechanisms triggers intracellular molecular signalling pathways, that promote beta-cell proliferation and differentiation, leading to an increase in the pool of endocrinocytes in the pancreas and enhancing their functional activity.

Aim: to identify quantitative distribution patterns of c-Kit protein with high and low expression levels in endocrinocytes and pancreatic exocrinocytes in rats’ streptozotocin-induced diabetes.

Materials and methods. The study was conducted on 20 white Wistar rats, which were divided into 2 groups of 10 animals each. Animals of group 1 were included in the control (intact) group. To model experimental diabetes mellitus, animals of group 2 were injected intraperitoneally with streptozotocin (Sigma-Chemical, USA) at a dose of 50 mg/kg dissolved in 0.5 ml of 0.2 M citrate buffer pH = 4.5.

Results. The study of immunoreactivity to c-Kit protein in intact rats and in diabetic animals showed the presence of patterns with high and low expression levels both in endocrinocytes of pancreatic islets and in the exocrine part of the pancreas. Among the endocrinocytes of intact rats, cells with a high level of c-Kit protein expression prevailed and in the exocrine part of the pancreas – cells with a low level of protein expression. The development of diabetes resulted in a significant increase in the number of c-Kit-immunopositive alpha cells with a low level of protein expression (3.6-fold, p < 0.001), as well as pancreatic exocrinocytes (by 38 %, p < 0.001). At the same time, the formation of diabetes did not lead to changes in c-Kit protein concentration in all pancreatic cells with a low level of c-Kit protein expression.

Conclusions. c-Kit-immunopositive cells of the pancreas form two patterns of cells – with a high level of c-Kit protein expression, and with a low level of its expression. In intact animals, endocrinocytes with a high level of c-Kit protein expression predominate, and in the exocrine part of the pancreas – cells with and low level of protein expression. Alpha-endocrinocytes of intact rats have a 30 % higher (p < 0.001) c-Kit protein expression level compared to beta-cells and exocrinocytes. The development of diabetes in rats was accompanied by a significant increase in the number of c-Kit-immunopositive beta cells with a high level of protein expression, as well as an increase in the number of alpha cells and exocrinocytes with both high and low levels of c-Kit protein expression. In the pattern of beta cells with a high level of protein expression in diabetes, an increase in the concentration of the c-Kit protein was observed (by 17 %, p < 0.001) compared to intact endocrinocytes, while in alpha cells and exocrinocytes a similar pattern of the concentration of the c-Kit protein was observed significantly decreased (by 44 % and 30 %, respectively).