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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 andThe 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.

Background and aim Metabolic disturbances are known for their increasing epidemiological importance. Ilex paraguariensis presents a potential option for mitigating lipid metabolism imbalance. However, most of the literature to date has not considered sex bias. This study aimed to evaluate the effect of Ilex paraguariensis on the metabolism of different adipose tissue depots in males and females. Experimental procedure After ovariectomy, female Wistar rats received daily treatment with the extract (1 g/kg) for forty-five days. Biochemical serum parameters and tissue metabolism were evaluated. Oxidation, lipogenesis and lipolysis were evaluated in brown, white visceral, retroperitoneal and gonadal adipose tissues. Results and conclusion The results showed that treatment with the extract led to a reduced weight gain in ovariectomised females in comparison to control. The triglyceride concentration was decreased in males. Glucose oxidation and lipid synthesis in visceral and retroperitoneal adipose tissues were restored in ovariectomised females after treatment. The response to epinephrine decreased in visceral adipose tissue of control males; however, lipolysis in females did not respond to ovariectomy or treatment. These findings highlight the enormous potential effects of I. paraguariensis on lipid metabolism, modulating lipogenic pathways in females and lipolytic pathways in males. Furthermore, the sex approach applied in this study contributes to more effective screening of the effects of I. paraguariensis bioactive substances., Graphical abstract Image 1, Highlights • Ilex paraguariensis reduced weight gain of ovariectomy females to control levels • Serum triglycerides decreased in male and estrogen-deficient female after treatment • Treatment restored glucose oxidation and lipogenesis of estrogen-deficient females • I. paraguariensis decreased lipolysis response in visceral adipose tissue of males