Accumulating evidences showed metformin and berberine, well‐known glucose‐lowering agents, were able to inhibit mitochondrial electron transport chain at complex I. In this study, we aimed to explore the antihyperglycaemic effect of complex I inhibition. Rotenone, amobarbital and gene silence of NDUFA13 were used to inhibit complex I. Intraperitoneal glucose tolerance test and insulin tolerance test were performed in db/db mice. Lactate release and glucose consumption were measured to investigate glucose metabolism in HepG2 hepatocytes and C2C12 myotubes. Glucose output was measured in primary hepatocytes. Compound C and adenoviruses expressing dominant negative AMP‐activated protein kinase (AMPK) α1/2 were exploited to inactivate AMPK pathway. Cellular NAD +/NADH ratio was assayed to evaluate energy transforming and redox state. Rotenone ameliorated hyperglycaemia and insulin resistance in db/db mice. It induced glucose consumption and glycolysis and reduced hepatic glucose output. Rotenone also activated AMPK. Furthermore, it remained effective with AMPK inactivation. The enhanced glycolysis and repressed gluconeogenesis correlated with a reduction in cellular NAD +/NADH ratio, which resulted from complex I suppression. Amobarbital, another representative complex I inhibitor, stimulated glucose consumption and decreased hepatic glucose output in vitro, too. Similar changes were observed while expression of NDUFA13, a subunit of complex I, was knocked down with gene silencing. These findings reveal mitochondrial complex I emerges as a key drug target for diabetes treatment. Inhibition of complex I improves glucose homoeostasis via non‐AMPK pathway, which may relate to the suppression of the cellular NAD +/NADH ratio.

The aim of this study was to investigate the effect of testosterone and oestrogen on regulating organic cation transporters (Octs) and multidrug and toxin extrusions (Mates) expression in the kidney of mice and urinary excretion of metformin. 8 week‐old male db/db mice were treated with estradiol (5 mg/kg), testosterone (50 mg/kg) or olive oil with same volume. Metformin (150 mg/kg) was injected in daily for successive 7 days. Plasma, urine and tissue concentrations of metformin were determined by liquid chromatography‐tandem mass spectrometry (LCMS) assay. Western blotting and Real‐time PCR analysis were successively used to evaluate the renal protein and mRNA expression of Octs and MATEs. After treatment, the protein expression of Mate1 and Oct2 in testosterone group was significantly increased than those in control group (both P < 0.05). The protein expression of Mate1 and Oct2 in estradiol group was significantly reduced by 29.4% and 43.3%, respectively, compared to those in control group (all P < 0.05). These data showed a good agreement with the change in mRNA level (all P < 0.05). The plasma metformin concentration (ng/ml) in mice treated with estradiol was significantly higher than control and testosterone group (677.56 ± 72.49 versus 293.92 ± 83.27 and 261.46 ± 79.45; P < 0.01). Moreover, testosterone increased the metformin urine excretion of mice while estradiol decreasing (both P < 0.01). Spearman correlation analysis showed that gonadal hormone was closely associated with Mate1 and Oct2 expression and metformin urine excretion in db/db mice (all P < 0.05). Testosterone and oestrogen exerted reverse effect on metformin urinary excretion via regulating Octs and Mates expression in the kidney of mice.

OBJECTIVES: Cystatin C is growing to be an ideal indicator for renal function and cardiovascular events. The aim of this study was to investigate the relationship between serum Cystatin C levels and the prognosis of diabetic foot ulcerations (DFU). METHOD: Totally 1012 patients with Type 2 diabetes were recruited and divided into two groups: non-diabetic-foot group (NDF, n = 865, 85.5%) and diabetic foot ulcer group (DFU, n = 147, 14.5%). After 1 year follow-up, the patients with DFU were grouped into healing group (n = 110, 74.8%) and non-healing group (n = 37, 25.2%) according to the clinical prognosis. Clinical characteristics and the impact factors of ulcer healing were compared and analyzed. RESULTS: Compared to the cured group, patients in non-healing group were older, had long diabetic duration and significantly higher serum Cystatin C concentrations in DFU (P < 0.01). Multiple logistical regression analysis revealed that Cystatin C was an independent impact factor for non-healing rate of DFU (b =-1.277, P < 0.01). After adjusting for age, duration, renal function, Cystatin C was still linked with increased risk of undesirable DFU outcome (OR = 7.279, 95% CI: 1.299-40.784, P < 0.05). By dividing patients into quar-tiles according to Cystatin C, a downward trend in healing rate was found with increased quartile of serum Cystatin C, there are significant lower healing rate was found in fourth group which was only 57.9% compared with other three groups (P < 0.01). The oddis ratio (OR) analysis showed that the risk of undesirable outcome of DFU in Quartile 4 increased significantly (OR = 4.554, 95% CI: 3.14-5.12, P < 0.05) compared with that of Quartile 1. ROC analysis further indicated that the optimal cutoff of Cystatin C to predict the poor prognosis of DFU was 1.35 mg/L (P < 0.01) with 79.3% of sensitivity and nearly 62% of specificity. CONCLUSIONS: There is a strong and independent association between serum Cys-tatin C and diabetic foot ulceration prognosis, and Cystatin C > 1.35 mg/L predicts more than 6-fold increased risk of incurable foot ulceration. OBJECTIVES: Recent studies highlight a critical interaction between adipocyte fatty acid binding protein (A-FABP) and cardiovascular disorders. However, relationships between serum A-FABP with subclinical atherosclerosis in normal glucose tolerance subjects remain unknown. The study aimed to evaluate the association of serum A-FABP with carotid intima-media thickness (C-IMT) in a Chinese population with normal glucose tolerance. METHOD: 2253 cardiovascular disease-free participants with normal glucose tolerance aged from 20 to 78 years old (835 men, 1418 women) from the Shanghai Obesity Study were enrolled. Serum A-FABP levels were measured by a sandwich enzyme-linked immunosorbent assay. B-mode ultrasound was used to assess C-IMT. RESULTS: Serum A-FABP level was significantly higher in women than men (P < 0.001). Partial correlation analysis showed that serum A-FABP was associated with C-IMT in men, premenopausal and postmenopausal women after adjusting...

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