The Effects Of Cigarette Smoke On Hyperglycemia And The Diabetes-Related Vascular Diseases

Objective:Cigarettes smoking may disturb the function of islet cells,the secretion of insulin and the expression of liver glycogen synthase in rats,and melatonin might exert a protective effect in the process.Methods:The experimental animal smoking device was applied to smoking treatment in rats.The blood glucose values were monitored,and the insulin secretion and glycogen synthesis related to sugar metabolism were also studied in the level of protein expression and histopathology.The β cells and hepatocytes were also used to analyze the effect of cigarettes smoking in vitro.Results:In the current 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 cells 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).Conclusion:The current study uncovered potentially underling mechanisms related to the association between smoking and diabetes.In addition,it reported that melatonin effectively protected against smoking induced glucose metabolic alterations and the signal transduction pathway of melatonin is mainly mediated by its MT2 receptor.Objective:The mechanism of inflammation and oxidative stress involved in diabetic vascular diseases.And the potential protection of melatonin was used for vascular diseases.Methods:The experimental study of Sprague-Dawley rats in vivo and smooth muscle cells(SMCs)and vascular endothelial cells(VECs)in vitro were used to study the diabetes-related vascular diseases.The experimental groups were as follows:high glucose group,high glucose plus melatonin group,normal control group and melatonin control group.The expression of inflammatory factors,anti-inflammatory factors and antioxidant enzymes were detected by RT-PCR and western blot;the function and morphological changes of aorta and coronary arteries were analyzed by tissue pathology.Results:Sprague-Dawley rats experiment demonstrated that hyperglycemia increased ROS level and decreased superoxide dismutase(SOD)and nitric oxide synthase(NOS)activities.Moreover,the cardiovascular dysfunction was indicated by the disorder in eNOS phosphorylation activates and overexpression of inflammatory factors.In high glucose group,SMCs and VECs apoptosis levels increased with high concentrations of glucose;Western blot and RT-PCR analyses demonstrated that the inflammatory factor osteopontin(OPN)and intercellular cell adhesion molecule-1(ICAM1)and the inhibitory p-eNOS(Thr495)were increased by high glucose;the anti-inflammatory nuclear factor E2-related factor 2(Nrf2)and the activating p-eNOS(Ser1177)were decreased;and P38 involved the signal transduction pathway regulated by high glucose.Melatonin exerts cardiovascular protective properties via its free radical scavenging activity and anti-inflammatory effects in diabetes.Additionally,melatonin preserved elastic fibers integrity and attenuated pathological calcification and myocardial infarction in the cardiovascular system of diabetic rats.Conclusion:High glucose induced inflammatory and oxidative damage in vitro and in vivo,which could be a key factor in diabetic angiopathies.Melatonin could play a protective role by reducing inflammatory response and oxidative damage.