Lower circulating irisin levels in type 2 diabetes mellitus patients with chronic complications: A meta-analysis.

Purpose: The aim of this study was to provide evidence of the differences in circulating irisin levels between type 2 diabetes mellitus (T2DM) patients with and without chronic complications. Methods: We performed a meta-analysis to compare circulating irisin levels between different groups. Literature search was conducted in PubMed, Cochrane Library, Embase, WanFang, and China National Knowledge Infrastructure databases from inception through December 2022. Random effects model and standard mean difference (SMD) was used to calculate the pooled outcomes with 95 % confidence intervals (CIs). Results: Forty-two studies that matched the inclusion criteria were analyzed. Circulating irisin levels were significantly lower in T2DM patients with chronic complications than those in T2DM patients without chronic complications (SMD: -1.43; 95 % CI: -1.76 to -1.09; p < 0.00001) and healthy control group (SMD: -2.40; 95 % CI: -3.02 to -1.77; p < 0.00001). Moreover, irisin levels further decrease with the aggravation of complications in T2DM patients with diabetic nephropathy or diabetic retinopathy. Conclusion: Compared with T2DM patients without chronic complications, T2DM patients with chronic complications had lower circulating irisin levels. In addition, irisin levels were negatively correlated with the severity of chronic complications.

Effects of ginkgo leaf tablet on the pharmacokinetics of rosiglitazone in rats and its potential mechanism.

CONTEXT: Ginkgo leaf tablet (GLT), a traditional Chinese herbal formula, is often combined with rosiglitazone (ROS) for type 2 diabetes mellitus treatment. However, the drug-drug interaction between GLT and ROS remains unknown. OBJECTIVE: To investigate the effects of GLT on the pharmacokinetics of ROS and its potential mechanism. MATERIALS AND METHODS: The pharmacokinetics of 10 mg/kg ROS with 100/200 mg/kg GLT as single-dose and 10-day multiple-dose administration were investigated in Sprague-Dawley rats. In vitro, the effects of GLT on the activity of CYP2C8 and CYP2C9 were determined in recombinant human yeast microsomes and rat liver microsomes with probe substrates. RESULTS: The t1/2 of ROS increased from 2.14 ± 0.38 (control) to 2.79 ± 0.37 (100 mg/kg) and 3.26 ± 1.08 h (200 mg/kg) in the single-dose GLT administration. The AUC0-t (139.69 ± 45.46 vs. 84.58 ± 39.87 vs. 66.60 ± 15.90 h·µg/mL) and t1/2 (2.75 ± 0.70 vs. 1.99 ± 0.44 vs. 1.68 ± 0.35 h) decreased significantly after multiple-dose GLT treatment. The IC50 values of quercetin, kaempferol, and isorhamnetin, GLT main constituents, were 9.32, 7.67, and 11.90 µmol/L for CYP2C8, and 27.31, 7.57, and 4.59 µmol/L for CYP2C9. The multiple-dose GLT increased rat CYP2C8 activity by 44% and 88%, respectively. DISCUSSION AND CONCLUSIONS: The metabolism of ROS is attenuated in the single dose of GLT by inhibiting CYP2C8 and CYP2C9 activity, and accelerated after the multiple-dose GLT treatment via inducing CYP2C8 activity in rats, indicating that the clinical dose of ROS should be adjusted when co-administrated with GLT.

Effects of the total flavonoid extracts and the monomers of Daphne genkwa on CYP2C8 activity.

This study aimed to assess the effects of total flavonoid extracts (TFDG) and the monomers of Daphne genkwa on the CYP2C8 activity in vitro and in vivo.The 50% inhibitory concentration (IC50) values were used to determine the inhibitory effect of TFDG and its four monomers for the CYP2C8 activity by recombinant human CYP2C8 (RHCYP2C8) yeast microsome system in vitro, and the volume per dose index (VDI) was predicted the potential inhibition in vivo. The effects of multiple-dose administration of TFDG on the pharmacokinetic parameters of rosiglitazone in rats were evaluated.The IC50 values of apigenin, luteolin, hydroxy-genkwanin, genkwanin, and TFDG were 7.27 µmol/L, 11.9 µmol/L, 28.1 µmol/L, 127 µmol/L, and 13.4 µg/mL, respectively. The VDI values of apigenin and TFDG were 2.15 L and 6.60 L. In vivo study, compared with the control group, the elimination phase half-life and mean residence time in the TFDG treatment group were significantly increased by 96.9% and 106.8% (p <.05), respectively.Apigenin showed a moderate inhibitory effect on the CYP2C8 activity in vitro, while the other three monomers were weak inhibitors. TFDG had a strong inhibitory effect on CYP2C8 in vitro and in vivo, and also inhibited the metabolism of rosiglitazone in rats.