Mitofusin 2 (Mfn2) is a dynamin-like protein anchored in the outer mitochondrial membrane that plays a crucial role in ensuring optimal mitochondrial morphological homeostasis. It has been shown that reduced expression of Mfn2 is associated with insulin resistance, but the mechanism is still unclear. We investigated whether Mfn2 deficiency leads to impaired insulin sensitivity via elevated oxidative stress. L6 skeletal muscle cells were treated with palmitate and Mfn2 expression was repressed by transfection with antisense Mfn2. Levels of antioxidant enzymes, reactive oxygen species (ROS), the phosphorylation of c-Jun N-terminal Kinase (JNK) and nuclear factor-κB (NF-κB) and the mitochondrial membrane potential (Δψm) were measured. The results showed palmitate-induced insulin resistance of skeletal muscle cells was accompanied by Mfn2 repression. Meanwhile, the cells had decreased Δψm and activity of antioxidant enzymes which could increase production of ROS, phosphorylation of JNK and NF-κB. When Mfn2 was up-regulated in palmitate-treated cells, oxidative stress and insulin resistance was alleviated. Furthermore, knock-down of Mfn2 in control cells enhanced oxidative stress. Mfn2 deficiency led to increased superoxide concentration and activation of JNK as well as NF-κB associated with insulin signaling. In conclusion, Mfn2 is a potent repressor for oxidative stress and regulation of Mfn2 expression may prove to be a potential method to circumvent insulin resistance.

No abstract

Mitofusin 2 (Mfn2) is a mitochondrial membrane protein that plays a role in mitochondrial fusion and metabolism in mammalian cells. Previous studies have reported a positive correlation between Mfn2 expression and insulin sensitivity in non‑diabetic and type 2 diabetic subjects. Thus, the aim of the present study was to investigate whether Mfn2 overexpression improves insulin sensitivity of high‑fat diet (HFD) rats and the possible underlying mechanisms. Male SD rats were randomly divided into four groups: negative control; HFD; HFD plus adenoviral vectors; and HFD plus adenoviral vectors encoding Mfn2. Following an 11‑week treatment protocol, the euglycemic‑hyperinsulinemic clamp technique was applied to evaluate insulin sensitivity in rats. The skeletal muscles from rats in each group were analyzed by real‑time PCR and western blot analysis to determine glucose transporter 4 (GLUT4) expression, translocation and relative translocation signaling. Consistent with Mfn2 repression and glucose intolerance, HFD downregulates GLUT4 expression at the mRNA and protein levels, while Mfn2 overexpression activates AMP‑activated protein kinase (AMPK), increases GLUT4 expression and translocation and improves insulin resistance in the skeletal muscles of HFD rats. Results of the present study indicate that Mfn2 overexpression improves insulin sensitivity and may regulate GLUT4 translocation in an AMPK‑dependent manner in the skeletal muscles of HFD rats. This study is likely to provide insight into the unique role of Mfn2 in promoting glucose uptake, leading to modulation of GLUT4 translocation signaling and maintenance of glucose homeostasis in vivo.

BackgroundIncreased lipid accumulation and mitochondrial dysfunction within skeletal muscle have been shown to be strongly associated with insulin resistance. However, the role of mitofusion-2 (MFN2), a key factor in mitochondrial function and energy metabolism, in skeletal muscle lipid intermediate accumulation remains to be elucidated.ResultsA high-fat diet resulted in insulin resistance as well as accumulation of cytosolic lipid intermediates and down-regulation of MFN2 and CPT1 in skeletal muscle in rats, while MFN2 overexpression improved insulin sensitivity and reduced lipid intermediates in muscle, possibly by upregulation of CPT1 expression.ConclusionsMFN2 overexpression can rescue insulin resistance, possibly by upregulating CPT1 expression leading to reduction in the accumulation of lipid intermediates in skeletal muscle. These observations contribute to the investigations of new diabetes therapies.

No abstract

Two windmill-like Ag3Cu5 alkynyl clusters were synthesized and characterized. They display novel PL and ECL properties, which could be modified by changing the substituent on the alkynyl ligands. According to the study of electrochemical behaviours, ECL behaviours and ECL emission spectra of the Ag3Cu5 clusters, a possible ECL mechanism was proposed.

No abstract

A simple, rapid, reproducible and sensitive method based on CE with electrochemical detector was developed for the simultaneous determination of five thyreostatics including 2-thiouracil (TU), 6-methyl-2-thiouracil (MTU), 6-propyl-2-thiouracil (PTU), 6-phenyl-2-thiouracil (PhTU) and methimazole (TAP) in animal feeds. A home-made wall-jet electrochemical detector with a 300 microm diameter platinum-disk-working electrode was equipped at the end of separation capillary and used to detect oxidation currents of these thyreostatics. Under the optimum experimental conditions, TU, MTU, PTU, PhTU and TAP could be well separated within 15 min at the separation voltage of 16 kV in 20 mmol/L sodium borate buffer (pH 9.2). The detection limits (S/N=3) of the five thyreostatics in animal feeds were found to be 7.6 microg/kg for TAP, 25 microg/kg for PTU, 15 microg/kg for PhTU, 18 microg/kg for TU and 20 microg/kg for MTU by the developed CE with electrochemical detector method coupled with solid-phase extraction sample pretreatment technique.