The relationship between the morphofunctional state of pancreatic insular apparatus and islet fibrosis in old rats under alloxan-induced diabetes and alpha-lipoic acid correction

Abstract

The scientific data on age-related changes in the insular apparatus of the pancreas are contradictory, including age-related insular fibrosis. There are some questions about the relationship between different pathomorphological changes in the insular apparatus and the possibility of their pharmacological correction with antioxidants, for example, alpha-lipoic acid, proved for treatment of diabetic cardiomyopathy and polyneuropathy. The aim of this study is to identify the relationship between the morphofunctional state of pancreatic insular apparatus and islet fibrosis in old rats with alloxan-induced diabetes and its correction using alpha-lipoic acid. Materials and methods. The experiment was conducted on 40 white male Wistar rats, which were divided into 4 groups: 1st — young intact animals 6 months old (n=10), 2nd — control group, old intact animals 18 months old (n=10), 3rd — old animals 18 months old with experimental diabetes (n=10), 4th — old animals 18 months old with experimental diabetes mellitus and administration of alpha-lipoic acid (n=10). Diabetes mellitus was designed with 3-times intraperitoneal injections of alloxan solution at a total dose of 170 µg/kg of animal weight. Alpha-lipoic acid was administered intramuscularly at a dose of 4 mg/100g of animal weight for 30 days. A morphological investigation of the pancreas was conducted, followed by immunohistochemical staining for insulin, as well as an assessment of the histotopographic localization of collagen. The obtained data were processed by mathematical statistics. Results. Decrease in the functionality of the pancreatic insular apparatus is due to a decrease in the number of beta-cells and an increase in fibrotic changes in it as a result of physiological aging, which was confirmed by an increase in the level of glucose in the blood plasma and a decrease in insulin expression in the islets. Alloxan diabetes exacerbated these changes. Administration of alpha-lipoic acid to aged animals with experimental diabetes contributed to an increase in the number of islets, their cellularity, the content of islet beta cells and their insulin-producing activity, a decrease in blood glucose levels and the severity of fibrotic changes in the islets. Conclusion. In this study, it was shown for the first time that the administration of alpha-lipoic acid, which has an antioxidant capacity, caused a decrease in islet fibrosis in old animals with diabetes due to an increase in insulinocytes in the islet and a decrease in glucose concentration. Thus, alpha-lipoic acid has not only antidiabetic, but also geroprotective and antifibrogenic effects in old rats with alloxan-induced diabetes.