The influence of plaferon LB on regenerative processes in the pancreas in an alloxan-induced diabetes rat model

Irakli Latsabidze, Elene Janberidze, Manana Kakabadze, Neli Didebulidze, Tamar Machavariani


Background: The ability of dysfunctional β-cells lesion to regulate blood glucose levels can be normalized in by increasing the mass of existing β-cells in the pancreas. Study of regenerative processes in Diabetes Mellitus and finding new ways to activate β-cells precursors is of great theoretical and practical interest.

Methods: Using the methods of light, electron -microscopic, immunohistochemistry, electron-morphometric researches pancreas was studied in the experimental model of diabetes. In the present study, the influence of amniotic derived peptide (Plaferon LB) on renewal processes was investigated in the pancreas of rats with Alloxan-induced diabetes. From a total of 90 Wistar laboratory rats, 30 received an Alloxan injection to induce diabetes and undergo  treated one month later with Plaferon LB for ten days (Alloxan/Plaferon LB-treated group), 30 received an Alloxan injection but no subsequent treatments (Alloxan-treated group), and a control group of 30 rats (control group).

Results: Dystrophic and necrotic changes were detected in the pancreatic β-cells following the induction of diabetes with Alloxan, and several alterations were observed in the vascular system of the islets. Special emphasis was made on display of extra-islet cells during the experiment. Data obtained suggest that extra-islet cells exist in the rats pancreas with Alloxan diabetes in the different degree of maturation. Immunohistochemistry researches showed, that in Alloxan/Plaferon LB-treated rats pancreas cells adjacent to the duct epithelium and islets endothelial cells strongly expressed endothelial, hemopoetic and stem cell marker CD34. Cytokeratin CK19 and insulin were manifested in proliferating duct and some acinar cells. Electron-morphometric analysis of insulin granules in the extra-islet isolated β-cells showed increased proportion of light granules which is associated with increased insulin secretion.Results suggest that Plaferon LB: 1) promotes a decrease in the blood glucose level, 2) helps to stabilize oxidative metabolism in the vascular system and to decrease the intensity of endotheliocite injury, 3) encourages the maturation and differentiation of precursor cells, and 4) induces the renewal of β-cells in the pancreas of rats with Alloxan-induced diabetes.

Conclusions: Experimental results gave possibility to hypothesis, that the cells which can potentially differentiate into β-cells are extra-islet cells. Immunohistochemic and electron-morphometric investigation have shown, that damaged pancreas has capacity of generating new β-cells from ducts, exocrine or stem cells after activation with external stimuli. Presumably Plaferon LB takes part in the renewal processes of β-cells. However, these effects of Plaferon LB were not found to be sufficient to compensate for insulin deficiency.


Pancreas; β-cells; Precursor cells; Alloxan; Plaferon LB; Rats

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