Yapislar Hande, Haciosmanoglu Ebru, Sarioglu Turkan, Degirmencioglu Sevgin, Sogut Ibrahim, Poteser Michael, Ekmekcioglu Cem
Department of Physiology, Faculty of Medicine, Acibadem Mehmet Ali Aydinlar University, 34684 Istanbul, Turkey.
Department of Biophysics, Faculty of Medicine, Bezmialem Vakif University, 34093 Istanbul, Turkey.
Life (Basel). 2022 Apr 12;12(4):574. doi: 10.3390/life12040574.
Insulin resistance is associated with a pro-inflammatory state increasing the risk for complications in patients with type 2 diabetes mellitus (T2DM). In addition to its chronobiotic effects, the pineal hormone melatonin is known to exert anti-inflammatory and antioxidant effects. Melatonin was also suggested to affect insulin secretion. The aim of this study was therefore to investigate the effect of melatonin on inflammation in diabetic rats and to study the possible involvement of the melatonin receptor, MT2.
Male Sprague Dawley rats were randomly divided into four experimental groups ( = 10 per group): (1) control, (2) streptozotocin/nicotinamide induced diabetes type 2 (T2DM), (3) T2DM treated with melatonin (500 µg/kg/day), and (4) T2DM treated with melatonin (500 µg/kg/day for 6 weeks) and the selective MT2 receptor antagonist luzindole (0.25 g/kg/day for 6 weeks). Blood samples were taken for biochemical parameters and various tissue samples (liver, adipose tissue, brain) were removed for immunohistochemistry (IHC), Western blot (WB), and Q-PCR analyses, respectively.
Melatonin significantly reduced increased blood levels of liver transaminases (AST, ALT), blood urea nitrogen (BUN), triglyceride, very low-density lipoprotein (VLDL), and cholesterol in diabetic rats with luzindole treatment partly reversing this effect regarding the lipids. Furthermore, the liver and adipose tissues of T2DM rats treated with melatonin showed lower expression of the inflammatory markers IL-1β, IL-6, TNF-α, and NF-κB as compared to the T2DM group without melatonin. The results also showed that the MT2 receptor is at least partly involved in the protective effects of melatonin.
Our results suggest that melatonin exerts relevant anti-inflammatory effects on various tissues in type 2 diabetic rats.
胰岛素抵抗与促炎状态相关，会增加2型糖尿病（T2DM）患者发生并发症的风险。松果体激素褪黑素除了具有调节生物钟的作用外，还具有抗炎和抗氧化作用。褪黑素也被认为会影响胰岛素分泌。因此，本研究的目的是探讨褪黑素对糖尿病大鼠炎症的影响，并研究褪黑素受体MT2可能发挥的作用。
雄性Sprague Dawley大鼠随机分为四个实验组（每组n = 10）：（1）对照组，（2）链脲佐菌素/烟酰胺诱导的2型糖尿病（T2DM）组，（3）用褪黑素（500μg/kg/天）治疗的T2DM组，以及（4）用褪黑素（500μg/kg/天，持续6周）和选择性MT2受体拮抗剂鲁辛朵（0.25g/kg/天，持续6周）治疗的T2DM组。采集血样检测生化参数，并分别取各种组织样本（肝脏、脂肪组织、脑）进行免疫组织化学（IHC）、蛋白质印迹法（WB）和定量聚合酶链反应（Q-PCR）分析。
褪黑素显著降低了糖尿病大鼠肝脏转氨酶（AST、ALT）、血尿素氮（BUN）、甘油三酯、极低密度脂蛋白（VLDL）和胆固醇的升高水平，鲁辛朵治疗部分逆转了褪黑素对脂质的这种作用。此外，与未用褪黑素治疗的T2DM组相比，用褪黑素治疗的T2DM大鼠的肝脏和脂肪组织中炎症标志物IL-1β、IL-6、TNF-α和NF-κB的表达较低。结果还表明，MT2受体至少部分参与了褪黑素的保护作用。
我们的结果表明，褪黑素对2型糖尿病大鼠的各种组织具有显著的抗炎作用。
