Objective
Hepatic insulin resistance is a major initiating factor for type 2 diabetes mellitus. In previous study, Gegen Qinlian Decoction containing berberine could enhance hepatic insulin sensitivity by SIRT1-dependent deacetylation of FOXO1. However, it is not clear whether berberine also can improve hepatic insulin sensitivity by SIRT1/FOXO1 pathway. This study aimed to evaluate the efficacy of berberine for improving hepatic insulin resistance and the possible molecular mechanisms involved.
Methods
In vitro, HepG2 cells were induced with palmitic acid, and glycogen synthesis was examined. In vivo, a high-fat diet (HFD)-fed mouse model was established, and metabolic parameters were assessed. The expressions of miR-146b and sirtuin 1 (SIRT1) in liver were also examined. The relationship between miR-146b and SIRT1 was examined by the dual-luciferase reporter gene assay.
Results
Serum biochemical parameters, such as glucose and HOMA-IR index, were increased in HFD mice; miR-146b and SIRT1 were abnormally expressed in HFD mice and palmitic acid-treated HepG2 cells. Interestingly, berberine reduced body weight and caused a significant improvement in glucose tolerance and HOMA-IR index without altering food intake in mice. Overexpression of miR-146b abolished the protective effect of berberine on palmitic acid-induced impaired glycogen synthesis in HepG2 cells. Luciferase assay showed that miR-146b directly targeted SIRT1.
Conclusion
The present findings suggest that berberine could attenuate hepatic insulin resistance through the miR-146b/SIRT1 pathway, which may represent a potential therapeutic target for the prevention and treatment of metabolic diseases, particularly diabetes.
Broad-spectrum antibiotics are the conservative treatment for tubo-ovarian abscess (TOA) or pelvic abscess, but the failure rate of antibiotic therapy remains higher in patients with a larger abscess. The present study aimed to evaluate the clinical value of early laparoscopic therapy in the management of TOA or pelvic abscess. A total of 100 patients were enrolled and their medical records were retrospectively analyzed after excluding 6 patients with malignant diseases. Based on the treatment they had received, the patients were divided into a conservative treatment group (n=41) and an early laparoscopic treatment group (n=53). In the conservative treatment group, 21 patients (51.2%) finally received laparoscopic exploration (late laparoscopic treatment group), and 20 patients (48.8%) achieved a success of antibiotic therapy (successful antibiotic therapy group). The cut-off value of abscess size for predicting antibiotic treatment failure was determined using receiver operating characteristic curve analysis. Multivariate logistic regression analyses were used to explore the association between the clinical variables and antibiotic therapy failure in conservative treatment group. The durations of elevated temperature >38.0°C and hospitalization were significantly longer in the conservative treatment group than those in the early laparoscopic treatment group (all P<0.001). The patients in the late laparoscopic treatment group had a larger abscess size than those in the successful antibiotic therapy group (6.2±1.8 cm vs. 4.8±1.4 cm, P=0.008). An abscess diameter of 5.5 cm was obtained as the cut-off of antibiotic failure, and the sensitivity and specificity were 81.0 and 85.0%, respectively. An abscess diameter of ≥5.5 cm was independently associated with antibiotic failure (odds ratio=5.724; 95%CI: 2.025–16.182; P=0.001). In conclusion, early laparoscopic treatment was associated with a better clinical prognosis than conservative treatment and late laparoscopic therapy for TOA or pelvic abscess patients.
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