Modeling of gestational diabetes mellitus in animals: optimization of the streptozotocin administration regimen against the background of a high-fat diet

Background. Gestational diabetes mellitus (GDM) is a serious and widespread health problem. Analysis of existing animal models of GDM induced by a high-fat diet (HFD) and administration of streptozotocin, which destroys pancreatic β-cells, reveals significant differences in dosage and duration of drug administration.

Aim. Optimization of the protocol for administering streptozotocin to female C57BL/6 mice to model GDM accompanied by persistent hyperglycemia and impaired glucose tolerance during pregnancy for testing drugs.

Materials and Methods. Female C57BL/6 mice were kept on a HFD throughout the experiment. Before pregnancy, the mice were injected three or four times with STZ at a dose of 60 mg/kg. Body weight, feed and water intake, and blood glucose levels in the females were assessed, glucose tolerance test and pathomorphological analysis of the pancreas were performed, and the reproductive capacity of dams and survival of the offspring were assessed.

Results. Four consecutive injections of streptozotocin at a dose of 60 mg/kg contribute to the development of hyperglycemia and lead to an increase in blood glucose concentration in females in a glucose tolerance test during pregnancy and lactation. Animals exhibit more pronounced polydipsia, atrophic changes in the pancreatic endocrine system, as well as a tendency to reduce litter size and offspring survival. The use of three streptozotocin doses causes hyperglycemia, leading to an increase in the area under the curve in the glucose tolerance test only during pregnancy.

Conclusion. Three injections of streptozotocin at a dose of 60 mg/kg are sufficient to induce hyperglycemia and impaired glucose utilization in pregnant C57BL/6 mice fed a HFD. This administration regimen causes temporary metabolic disturbances and does not affect the reproductive function of animals, making it suitable for use as a model to assess the efficacy of hypoglycemic drugs that could be used in GDM treatment.

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