RESUMEN
OBJECTIVE: To investigate whether and how glucagon-like peptide-1 (GLP-1) can protect podocytes from apoptosis induced by advanced oxidative protein products (AOPPs). METHODS: Murine podocytes were stimulated with 200 µg/ml AOPP for 48 h in the presence or absence of GLP-1. Cell viability was assessed using the cell counting kit-8 assay. Podocyte apoptosis was detected by flow cytometry and Hoechst 33258 staining. Superoxide radical production was assayed using lucigenin-enhanced chemiluminescence, and Western blotting was used to measure expression of RAGE, NADPH oxidase subunits p47phox and gp91phox, as well as apoptosis-associated proteins p53, Bax, Bcl-2 and caspase-3. RESULTS: Incubating podocytes with AOPPs reduced cell viability, triggered changes in cell morphology and promoted apoptosis. GLP-1 partially inhibited AOPP-induced apoptosis, O2- overproduction, and AOPP-induced expression of RAGE. GLP-1 inhibited expression of p47phox and gp91phox in AOPP-treated podocytes, and it attenuated AOPP-induced expression of p53, Bax and cleaved caspase-3, whereas it restored expression of Bcl-2. CONCLUSION: GLP-1 partially inhibits AOPP-induced apoptosis in podocytes, perhaps by interfering with the AOPP-RAGE axis, decreasing oxidative stress and inhibiting the downstream p53/Bax/caspase-3 apoptotic pathway. GLP-1 may be a useful anti-apoptotic agent for early intervention in diabetic nephropathy.
Asunto(s)
Productos Avanzados de Oxidación de Proteínas/metabolismo , Apoptosis , Péptido 1 Similar al Glucagón/metabolismo , Productos Finales de Glicación Avanzada/metabolismo , Podocitos/metabolismo , Animales , Supervivencia Celular , Ratones , NADP/química , Estrés Oxidativo , Oxígeno/química , Podocitos/citología , Especies Reactivas de Oxígeno/metabolismo , Receptor para Productos Finales de Glicación Avanzada/metabolismo , Superóxidos/química , Proteína p53 Supresora de Tumor/metabolismoRESUMEN
OBJECTIVE: To explore the prevalence and risk factors for abnormal plasma liver enzymes in patients with type 2 diabetes mellitus. METHODS: Overweight or obese patients with type 2 diabetes were recruited from 60 tertiary and secondary hospitals in Guangdong Province between August 2011 and March 2012. The abnormal plasma liver enzymes was diagnosed as alanine aminotransferase >40 U/L and/or aspartate aminotransferase >40 U/L. Binary Logistic regression was used to assess the associations between abnormal plasma liver enzymes and associated risk factors. RESULTS: The abnormal plasma liver enzymes were detected in 709/3543 diabetics with overweight or obesity. And the prevalence of abnormal plasma liver enzymes was 20.0%. According to binary Logistic regression analysis, the presence of abnormal plasma liver enzymes was associated with male gender (OR = 1.603, 95%CI: 1.247-2.061), higher HbA1c(OR = 1.049, 95%CI: 1.005-1.096), higher body mass index (OR = 1.058, 95%CI: 1.014-1.103), higher waist circumference (OR = 1.019, 95%CI: 1.006-1.032), higher triglyceride level (OR = 1.053, 95%CI: 1.008-1.100), adiposis hepatica (OR = 1.543; 95%CI: 1.244-1.914), regular exercises (OR = 0.591, 95%CI: 0.472-0.740) and diet control (OR = 0.794, 95%CI: 0.635-0.993). CONCLUSIONS: There is a high prevalence of abnormal plasma liver enzymes in overweight/obese with diabetics. And decreasing the levels of HbA1c, body mass index, waist circumference and triglycerides, regular exercises and diet control may decrease its prevalence.