Female Wistar rats present particular glucose flux when submitted to classic protocols of experimental diabetes

Type 1 diabetes mellitus is a prevalent autoimmune disease worldwide. The knowledge of female particularities in metabolic dysfunction is of fundamental importance, leading to better choices for human therapy candidates. The aim of this study is to investigate the glucose flux peculiarities of female rats submitted to two classic experimental diabetes protocols.

Female Wistar rats, 60 days old, were used to evaluate biochemical and hormonal serum parameters, in addition to skeletal muscle and liver energy stocks and ¹⁴C-glucose and ¹⁴C-alanine flux. Two different protocols, multiple (25 mg/kg dose) and single (65 mg/kg dose) intraperitoneal streptozotocin, were compared considering the alterations presented 48 h and 30 days after the drug administration.

The results showed few indicators of muscle and liver metabolic imbalance. High-single streptozotocin dose promoted 97% and 41% lower glycogen levels in liver and muscle respectively. Multiple-low streptozotocin dose promoted 63% lower lipid synthesis in liver. After 30 days, diabetic animals presented hyperglycaemia in both protocols, 589.5 (529.3/642.3) mg/dL to high-single dose and 374.2 (339.3/530.6) mg/dL to multiple-low dose. However, they did not present lower insulin levels, alterations on muscle glucose uptake, nor higher hepatic gluconeogenesis.

In conclusion, this study demonstrates that females, at least Wistar rats, are less responsive to classic diabetes protocols established in literature, so mechanisms of experimental diabetes for females need more investigation. After which, therapeutic candidates should be evaluated in such a way sex bias does not present itself as a factor that hinders reproducibility in human studies.