A promising biological model of gestational diabetes mellitus with specific impairments of carbohydrate and lipid metabolism in rats

Relevance . Gestational diabetes mellitus (GDM) is the most common complication of pregnancy. The lack of a biological model of GDM complicates the search for a suitable pharmacotherapy and presents the challenge of developing a valid model of this disease. Objective . The objective of this study was to develop a biological model of GDM accompanied by metabolic disorders in pregnant rats by using a high-calorie diet in combination with tyloxapol as diabetogenic factors. Materials and methods . GDM was modeled by keeping pregnant female Wistar rats on a high-calorie diet for at least 7 weeks in combination with intraperitoneal administration of tyloxapol at doses of 200 and 400 mg/kg on various days of pregnancy. In parallel we evaluated the dose dependence of the effects of tyloxapol by its single intraperitoneal administration to non-pregnant female Wistar rats at doses of 200, 300, 400 mg/kg. Results . The study showed that the optimal combination of a high-calorie diet with the administration of tyloxapol at a dose of 200 mg/kg is optimal for GDM induction. In this case, there is a marked violation of glucose tolerance, an increase in the levels of glucose, total cholesterol, triacylglycerides and low-density lipoproteins in the blood serum. A pronounced embryoletal effect was observed with tyloxapol at a dose of 400 mg/kg. The use of tyloxapol at a dosage of 300 mg/ kg did not lead to a change in the registered parameters. Conclusion . The proposed biomodel demonstrates the main pathognomonic symptoms of GDM and may be useful in studying the mechanisms of development and searching new treatments for this pathology.