Melatonin attenuates smoking‐induced hyperglycemia via preserving insulin secretion and hepatic glycogen synthesis in rats

Abstract

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.

Melatonin safeguards against fatty liver by antagonizing TRAFs‐mediated ASK1 deubiquitination and stabilization in a β‐arrestin‐1 dependent manner

“…Melatonin has been reported to be an important regulator of NAFLD/NASH by previous studies . Moreover, melatonin modulates NAFLD‐associated disorders such as insulin resistance, obesity, diabetes, and endothelial dysfunction . However, the exact mechanism of melatonin in NAFLD is not fully understood.…”

Role of transforming growth factor β1 in the inhibition of gastric cancer cell proliferation by melatonin in vitro and in vivo

“…MLT is also synthesized in some peripheral organs including gastrointestinal organs (3) and skin (4,5), with higher levels than that noted in the serum. MLT exerts a variety of receptor-mediated or receptor-independent physiological functions (6): Regulation of the circadian rhythm, inhibition of the development of the reproductive system, regulation of bone growth, inhibition of tumorigenesis, regulation of the immune system, scavenging of free radical antioxidants, and exhibition of anti-inflammatory and neuroprotective effects (5,(7)(8)(9). A large number of studies have shown that MLT can inhibit a variety of malignancies such as gastric (10), liver (11), breast (12) and oral cancer (13) by promoting tumor cell apoptosis, arresting the cell cycle, inhibiting proliferation, regulating antitumor immunity, scavenging free radicals, and competitively inhibiting estrogen receptors.…”

Melatonin Uptake by Cells: An Answer to Its Relationship with Glucose?

“…Hence, recent studies point out the involvement of redox-related pathways, namely NADPH oxidase [ 177 ]. Similarly, the direct or indirect free radical-scavenging action of melatonin might also play a role in this context, as the indole protects glucotoxicity-mediated pancreatic islets cell death through either its own signaling or an antioxidant pathway [ 178 , 179 , 180 ]. More recently, insulin-like growth factor binding proteins, such as IGFBP3, which can modulate insulin signaling, have been linked to melatonin actions in other tissues [ 181 ] so they should not be ruled out in playing a role in melatonin-induced glucose homeostasis.…”