Department of Vascular Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
J Pineal Res. 2018 May;64(4):e12475. doi: 10.1111/jpi.12475. Epub 2018 Mar 25.
Epidemiology survey indicated that cigarette smoking is a risk factor of diabetes. However, the precise mechanisms remain to be clarified. In this study, we found that smoking caused metabolic malfunctions on pancreas and liver in experimental animal model. These were indicated by hyperglycemia, increased serum hemoglobin A1c level and decreased insulin secretion, inhibition of liver glycogen synthase (LGS), and hepatic glycogen synthesis. Mechanistic studies revealed that all these alterations were caused by the inflammatory reaction and reactive oxygen species (ROS) induced by the smoking. Melatonin treatment significantly preserved the functions of both pancreas and liver by reducing β cell apoptosis, CD68-cell infiltration, ROS production, and caspase-3 expression. The siRNA-knockdown model identified that the protective effects of melatonin were mediated by melatonin receptor-2 (MT2). This study uncovered potentially underlying mechanisms related to the association between smoking and diabetes. In addition, it is, for first time, to report that melatonin effectively protects against smoking-induced glucose metabolic alterations and the signal transduction pathway of melatonin is mainly mediated by its MT2 receptor. These observations provide solid evidence for the clinically use of melatonin to reduce smoking-related diabetes, and the therapeutic regimens are absent currently.
流行病学调查表明，吸烟是糖尿病的一个危险因素。然而，其确切机制仍有待阐明。在本研究中，我们发现吸烟在实验动物模型中引起了胰腺和肝脏的代谢功能紊乱。这些变化表现为高血糖、血清血红蛋白 A1c 水平升高和胰岛素分泌减少、肝糖原合酶（LGS）抑制以及肝糖原合成减少。机制研究表明，这些改变都是由吸烟引起的炎症反应和活性氧（ROS）引起的。褪黑素治疗通过减少β细胞凋亡、CD68 细胞浸润、ROS 产生和 caspase-3 表达，显著地保护了胰腺和肝脏的功能。siRNA 敲低模型表明，褪黑素的保护作用是通过褪黑素受体-2（MT2）介导的。本研究揭示了吸烟与糖尿病之间相关的潜在机制。此外，这也是首次报道褪黑素能有效预防吸烟引起的葡萄糖代谢紊乱，而褪黑素的信号转导途径主要是由其 MT2 受体介导的。这些观察结果为临床上使用褪黑素来减少与吸烟有关的糖尿病提供了确凿的证据，而目前还没有有效的治疗方案。
