Physiology Department, Federal University of Rio Grande Do Sul, Sarmento Leite, Porto Alegre, Rio Grande do Sul, Brazil.
Physiology Department, Federal University of Rio Grande Do Sul, Sarmento Leite, Porto Alegre, Rio Grande do Sul, Brazil.
Biomed J. 2023 Jun;46(3):100539. doi: 10.1016/j.bj.2022.05.004. Epub 2022 May 20.
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 C-glucose and C-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.
1 型糖尿病是一种在全球范围内流行的自身免疫性疾病。了解女性在代谢功能障碍方面的特殊情况至关重要，这有助于为人类治疗候选者做出更好的选择。本研究旨在探讨两种经典实验性糖尿病模型中雌性大鼠葡萄糖通量的特点。
使用 60 天大的雌性 Wistar 大鼠评估血清生化和激素参数，以及骨骼肌和肝脏能量储备、C-葡萄糖和 C-丙氨酸通量。比较两种不同的方案，即多次（25mg/kg 剂量）和单次（65mg/kg 剂量）腹腔注射链脲佐菌素，比较两种方案在药物给药后 48 小时和 30 天呈现的变化。
结果显示肌肉和肝脏代谢失衡的指标很少。高单次链脲佐菌素剂量分别导致肝脏和肌肉糖原水平降低 97%和 41%。多次低剂量链脲佐菌素促进肝脏脂质合成降低 63%。30 天后，两种方案的糖尿病动物均出现高血糖，高单次剂量组为 589.5（529.3/642.3）mg/dL，多次低剂量组为 374.2（339.3/530.6）mg/dL。然而，它们并没有表现出较低的胰岛素水平、肌肉葡萄糖摄取的改变或更高的肝糖异生。
总之，本研究表明，女性（至少 Wistar 大鼠）对文献中建立的经典糖尿病模型的反应性较低，因此需要对女性的实验性糖尿病机制进行更多的研究。之后，应该以这样的方式评估治疗候选者，即性别偏见不会成为阻碍人类研究重现性的因素。
