Role of leucocytes in liver damage in experimental models of type 1 and 2 diabetes mellitus

Abstract

Diabetes mellitus is a metabolic disorder, which results from insufficient secretion of insulin and/or its action, thus leading to hyperglycemia. Liver damage is known to be among the most common complications of type 2 diabetes mellitus (T2D) and is common in T1D. Comparison of the leukocyte phenotypes in liver tissue with appropriate blood parameters may assess degree of liver damage and search for approaches to correction of liver destruction in diabetes mellitus. Therefore, we aimed for assessment of changes in liver injury markers in blood and the numbers of leucocytes (CD45+ cells), T lymphocytes (CD3+ cells) and macrophages in the liver in experimental models of types 1 and 2diabetes. The experiment was conducted on 30 male Wistar rats. Alloxan at the dose of 170 mg/kg of body weight was used for T1D modeling. To provide a model of T2D, streptozotocin and nicotinamide were injected at the doses of 65 mg/kg, and 110 mg/kg respectively. Intact animals were used as a comparison control. Biochemical, hematological, immunohistochemical and morphometrical methods were used in the study. In T1D and T2D groups, levels of glucose (10.88±0.47 mmol/l and 10.78±0.42 mmol/l) and glycosylated hemoglobin (6.73±0.78% and 6.60±0.20% correspondingly) were rather close to each other and exceeded the values of intact rats (5.20±0.40 mmol/l and 4.07±0.30%). At the same time, the increase in total leucocyte number and fraction of peripheral blood leucocytes against normal levels were more pronounced in the T2D group than in T2D group. In liver of rats from the both diabetic groups, increased numbers of sinusoidal cells, macrophages, CD45+ cells and CD3+ cells relative to intact rats were detected. However, in rats from T1D group, CD45+ cells were distributed, mainly, in the liver parenchyma, whereas in rats in T2D group they showed sinusoidal location. At a similar degree of increasing macrophage numbers, and total CD45+ cells number, higher counts of sinusoidal cells and CD3+ cells, located both in the parenchyma and perivascular area, were found in rats of T2DM group compared with this parameter in T1DM group. An increase in ALT activity confirms a more significant damage to liver cells in animals of the T2DM group, whereas, in T1DM group, an increased AST activity and a less pronounced increase in ALT activity indicate uniformly distributed cytolysis. The results of our study showed, that, despite similar hyperglycemia level, the inflammatory process at the level of the whole organism and local inflammatory process in the liver are more pronounced in the T2DM group. A more significant severity of inflammatory process and liver damage corresponds to increase in sinusoidal cells and CD3+ cell infiltration of liver tissue.

Keywords

• diabetes mellitus
• liver
• damage
• leukocytes
• lymphocytes
• macrophages