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Objective:To investigate the effects of liraglutide on the expressions of autophagy markers LC3B, LC3B mRNA and lipid deposition in myocardial tissue of rats with early diabetes mellitus.Methods:A total of 36 healthy male Wistar rats aged 4-5 weeks and weighing (l80-200) g were selected and divided into normal group (group NC, 10 rats) and model group (26 rats) according to random number table. Rats in the NC group were fed with routine diet and rats in the model group were given high glucose and high fat diet for 12 weeks. Rats in the model group were injected with streptozotocin into the abdominal cavity in a single dose of 25 mg/kg after molding. Rats in the model group were further divided into three groups: T2DM group (group DM/NS, 9 rats, given equal volume of saline) , liraglutide intervention group (group DM/LIR, 8 rats, injected with 100 μg/kg liraglutide twice daily) and Liraglutide and Chloroquine intervention group (group DM/LIR+CQ, 8 rats, injected with 100 μg/kg liraglutide twice daily, and injected with Chloroquine 50 mg/kg once every two days) . Rats in group NC were given equal volume of saline. At the end of 12 weeks, all the rats were tested blood glucose and anaesthetized to collect myocardial tissues to observe myocardial lipid deposition and fiber arrangement under light microscope after HE staining. The expressions of LC3B were detected by immunohistochemical method, and the expressions of LC3B mRNA were detected by real-time fluorescence quantitative polymerase chain reaction method. Differences among groups were compared by one-way analysis of variance, pairwise comparison was conducted by using LSD-t test, correlation was analyzed by Pearson correlation.Results:(1) Compared with group NC, the myocardial fibers arranged in disorder, and the ratio of myocardial foam cells/total cardiomyocytes were increased, the level of LC3B mRNA and LC3B were decreased in group DM/NS and DM/LIR+CQ (in group DM/NS: 2.18±0.90 vs 11.79±0.74, 2.03±0.10 vs 1.85±0.06, 194.18±10.19 vs 175.99±6.09, t=25.24, 4.69, 3.22, respectively; in group DM/LIR+CQ: 2.18±0.90 vs 11.24±1.29, 2.03±0.10 vs 1.89±0.08, 194.18±10.19 vs 176.73±7.82, t=17.56, 4.65, 3.99, respectively, all P<0.05) . There is no difference in above indicators (2.18±0.90 vs 1.29±0.60, 2.03±0.10 vs 2.01±0.20, 194.18±10.19 vs 201.27±11.35, t=2.20, 0.28, 1.40, respectively, all P>0.05) . (2) Compared with group DM/NS, the ratio of myocardial foam cells/total cardiomyocytes, the level of LC3B mRNA and LC3B were no difference in group DM/LIR+CQ ( t=1.09, 1.18,0.22, respectively, all P>0.05) . The ratio of myocardial foam cells/total cardiomyocytes was decreased, the level of LC3B mRNA and LC3B were increased in group DM/LIR (11.79±0.74 vs 1.29±0.60, 1.85±0.06 vs 2.01±0.20, 175.99±6.09 vs 201.27±11.35, t=31.86, 2.39, 5.82, respectively, all P<0.05) . (3) The significant negative correlation were observed between the ratio of myocardial foam cells/total cardiomyocytes and LC3B mRNA, LC3B levels (r=-0.977, -0.986, respectively, all P<0.05) . Conclusion:Liraglutide can protect the myocardial structure in early diabetic rats by increasing myocardial autophagy, reducing the number of myocardial foam cells, and improving the myocardial lipid deposition.
RESUMEN
Objective To observe the serum betatrophin levels in patients with type 2 diabetes mellitus (T2DM) and to explore the role of betatrophin in the pathogenesis of diabetic retinopathy (DR).Methods A total of 59 patients with T2DM (DM group) and 14 healthy controls (NC group) were enrolled in the study.Vision,slit lamp microscope,indirect ophthalmoscope,fluorescein fundus angiography were performed on all the subjects.According to the results of the examination combined with the international DR clinical staging criteria,the patients were divided into no DR (Non-DR) group,non-proliferative DR (NPDR) group,and proliferative DR (PDR) group,with 30,20 and 9 patients in each,respectively.The fasting blood glucose (FPG),insulin (FIN),C-peptide,glycated hemoglobin (HbA1c),total cholesterol (TC),triglyceride (TG),high-density lipoprotein (HDL-C),low-density lipid Protein (LDL-C) levels were detected.The level of betatrophin in serum was determined by enzyme-linked immunosorbent assay.The correlation between betatrophin and other indicators was analyzed by Spearman correlation.The influencing factors of PDR were analyzed by logistic regression.Results Compared with subjects in the NC group,the level of FPG (F=-4.316,P＜0.001),FIN (F=2.142,P=0.001),HbA1c (F=-5.726,P＜0.001),TC (t=3.609,P=-0.010),LDL-C (t=0.000,P=0.003),and betatrophin (F=-2.263,P=0.024) were significantly increased and HDL-C level (F=-3.924,P＜0.001) was decreases in the DM group.The difference of TG level between two groups was not statistically significant (F=-1.422,P=0.155).Compared with the Non-DR group and the NPDR group,the serum C-peptide (F=7.818,P=0.020) and betatrophin levels (F=1 2.141,P=0.002) were significantly increased in the PDR group.Spearman correlation analysis showed that the levels of betatrophin in the DM group was positively correlated to TC (r=0.304,P=0.019).The serum levels of betatrophin was positively correlated to body mass index in the Non-DR group (r=0.513,P=0.004).Furthermore,in the PDR group,a significant positive correlation was observed between the serum betatrophin levels and diastolic blood pressure (r=0.685,P=0.042).Logistic regression analysis showed that the duration of diabetes,serum C-peptide and betatrophin levels were risk factors for PDR.After controlling for the duration and serum C-peptide,the PDR risk for betatrophin levels great than or equal to 1.0 ng/ml was 12 times as much as betatrophin levels less than 1.0 ng/ml in T2DM patients.Conclusions The serum betatrophin content of patients with T2DM is abnormal.Betatrophin may be involved in the occurrence and development of PDR.