Department of Physiology, Faculty of Medicine, Beni-Suef University, Egypt.
Department of Biochemistry, Faculty of Pharmacy, Beni-Suef University, Egypt.
Steroids. 2019 Apr;144:1-7. doi: 10.1016/j.steroids.2019.01.004. Epub 2019 Jan 24.
Glucocorticoids (GCs) have various uses in the medicine in different specialties. However, GCs administration is usually accompanying with multiple side effects such as hyperglycemia and hyperlipidemia. Alpha lipoic acid (ALA) has been documented to posse anti-diabetic properties.
this study highlights the role of ALA in avoiding dexamethasone induced metabolic disturbance.
MATERIALS & METHODS: 30 rats were randomly divided into 5 groups: Group (1): Control group; Groups 3, 4, and 5: rats received dexamethasone 1 mg/kg/day for 10 days; Groups 2, 4, and 5: Rats received ALA 100 mg/kg/day all the duration of the study, 2 weeks before dexamethasone, or concomitant with dexamethasone respectively. For each rat, we collected blood samples for measurement of glucose, lipid profiles, adiponectin, irisin, and Phosphoinositide 3-kinase (PI3K). We also isolated gastrocnemius muscles for measurement of insulin receptor substrate-1(IRS-1), peroxisome proliferator-activated receptor γ coactivator 1 α(PGC1-α), and adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 1(APPL) gene expression.
Dexamethasone administration caused hyperglycemia, hyperlipemia, decrease the level of adiponectin, irisin, and PI3K besides decreasing the gene expression of IRS-1, PGC-1 α, and APPL1. ALA administration pre or concomitant to dexamethasone avoided these results.
ALA can prevent metabolic abnormalities induced by dexamethasone via PGC1α and APPL1 upregulation.
糖皮质激素(GCs)在不同专业的医学中有多种用途。然而,GCs 的应用通常伴随着多种副作用,如高血糖和高血脂。α-硫辛酸(ALA)已被证明具有抗糖尿病作用。
本研究强调了 ALA 在避免地塞米松引起的代谢紊乱中的作用。
30 只大鼠随机分为 5 组:第 1 组:对照组;第 3、4 和 5 组:大鼠每天接受地塞米松 1mg/kg,共 10 天;第 2、4 和 5 组:大鼠分别在接受地塞米松前 2 周或同时接受 ALA 100mg/kg,持续整个研究过程。每只大鼠采集血样,用于测量血糖、血脂谱、脂联素、鸢尾素和磷酸肌醇 3-激酶(PI3K)。我们还分离腓肠肌,用于测量胰岛素受体底物-1(IRS-1)、过氧化物酶体增殖物激活受体 γ 共激活因子 1α(PGC1-α)和衔接蛋白,磷酸酪氨酸相互作用 PH 结构域和亮氨酸拉链 1(APPL)基因表达。
地塞米松给药导致高血糖、高血脂,降低脂联素、鸢尾素和 PI3K 的水平,同时降低 IRS-1、PGC-1α和 APPL1 的基因表达。ALA 预先或同时给予地塞米松可避免这些结果。
ALA 通过上调 PGC1α 和 APPL1 可预防地塞米松引起的代谢异常。