title: Overexpression of mitofusin 2 improves translocation of glucose transporter 4 in skeletal muscle of high‑fat diet‑fed rats through AMP‑activated protein kinase signaling.
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.
authors: Department of Internal Medicine, Hebei Medical University, Shijiazhuang, Hebei 050017, PR China.
authors: Dexian
authors: D
authors: Kong
authors: Guangyao
authors: G
authors: Song
authors: Chao
authors: C
authors: Wang
authors: Huijuan
authors: H
authors: Ma
authors: Luping
authors: L
authors: Ren
authors: Qian
authors: Q
authors: Nie
authors: Xuemei
authors: X
authors: Zhang
authors: Kexin
authors: K
authors: Gan
mesh_terms: D055372:AMP-Activated Protein Kinases; D000818:Animals; D001786:Blood Glucose; D059305:Diet, High-Fat; D005227:Fatty Acids / Q000097:blood; D020558:GTP Phosphohydrolases; D015870:Gene Expression; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000235:genetics / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D024101:Mitochondrial Proteins / Q000235:genetics*; D018482:Muscle, Skeletal / Q000378:metabolism*; D021381:Protein Transport; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction
chemical_list: D001786:Blood Glucose; D005227:Fatty Acids; D051275:Glucose Transporter Type 4; D007328:Insulin; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D051057:Proto-Oncogene Proteins c-akt; D055372:AMP-Activated Protein Kinases; D020558:GTP Phosphohydrolases; C489710:Mfn2 protein, rat; D005947:Glucose