Distribution of vimentin in the human pancreatic islets in type 2 diabetes mellitus

Abstract

BACKGROUND: The expression of vimentin, an intermediate filament protein, has been detected in pancreatic islet cells of individuals with type 2 diabetes (T2D). Some studies have suggested that vimentin is expressed in differentiating β-cells during the restoration of their mass in diabetes. According to an alternative hypothesis, vimentin activation occurs in β-cells undergoing dedifferentiation and reprogramming into α-cells leading to a decrease in β-cell mass and T2D development. However, no studies have simultaneously evaluated the distribution of vimentin and alterations in the endocrine pancreas in T2D.

AIM: The study aimed to compare the distribution of vimentin in the human pancreatic islets with the characteristics of the endocrine pancreas in T2D and in the absence of carbohydrate metabolism disorders.

MATERIALS AND METHODS: Pancreatic autopsy samples from 13 individuals with T2D and 9 without carbohydrate metabolism disorders (comparison group) were investigated using double immunofluorescent staining with antibodies to vimentin and either insulin or glucagon. Using morphometric method and statistical analysis, the following parameters were measured and compared in individuals with T2D and those without carbohydrate metabolism disorders: distribution density of islets, average diameter of islets, relative area of β-cells, relative area of α-cells, percentage of islets containing vimentin-positive cells, average number of vimentin-positive cells per islet, percentage of vimentin-positive cells containing insulin, and percentage of vimentin-positive cells containing glucagon.

RESULTS: Vimentin-positive cells, some of which simultaneously contained insulin or glucagon, were detected in the pancreatic islets of individuals with T2D and those without carbohydrate metabolism disorders. Quantitatively, all parameters reflecting the distribution of vimentin were increased in individuals with T2D. Along with this, the relative area of α-cells increased, and the β-cell to α-cell ratio decreased in individuals with T2D.

CONCLUSIONS: An increase in the number of vimentin-positive cells in the pancreatic islets of individuals with T2D was associated with an increase in the relative area of α-cells. The activation of vimentin expression in islet cells was assumed to be related to the effect of hyperglycemia or other metabolic factors associated with diabetes and, probably, reflected the dedifferentiation and reprogramming processes of islet cells that are triggered in diabetes.

Keywords

pancreas / pancreatic islets / type 2 diabetes mellitus / vimentin / insulin / glucagon

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Funding

Правительство РФGovernment of the Russian Federation(123053000048-6)

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