title: Hepatic response to restoration of GLUT4 in skeletal muscle of GLUT4 null mice.
abstract: Expression of GLUT4 in fast-twitch skeletal muscle fibers of GLUT4 null mice (G4-MO) normalized glucose uptake in muscle and restored peripheral insulin sensitivity. GLUT4 null mice exhibit altered carbohydrate and lipid metabolism in liver and skeletal muscle. To test the hypothesis that increased glucose utilization by G4-MO muscle would normalize the changes seen in the GLUT4 null liver, serum metabolites and hepatic metabolism were compared in control, GLUT4 null, and G4-MO mice. The fed serum glucose and triglyceride levels of G4-MO mice were similar to those of control mice. In addition, the alternations in liver metabolism seen in GLUT4 nulls including increased GLUT2 expression and fatty acid synthesis accompanied by an increase in the oxidative arm of the pentose phosphate pathway were absent in G4-MO mice. The transgene used for GLUT4 restoration in muscle was specific for fast-twitch muscle fibers. The mitochondria hypertrophy/hyperplasia in all GLUT4 null skeletal muscles was absent in transgene-positive extensor digitorum longus muscle but present in transgene-negative soleus muscle of G4-MO mice. Results of this study suggest that the level of muscle GLUT4 expression influences mitochondrial biogenesis. These studies also demonstrate that the type and amount of substrate that muscle takes up and metabolizes, determined in part by GLUT4 expression levels, play a major role in directing hepatic carbohydrate and lipid metabolism.
authors: Department of Biochemistry, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors: Mollie
authors: M
authors: Ranalletta
authors: Xiu Quan
authors: XQ
authors: Du
authors: Yoshinori
authors: Y
authors: Seki
authors: Alan S
authors: AS
authors: Glenn
authors: Michael
authors: M
authors: Kruse
authors: Ariana
authors: A
authors: Fiallo
authors: Irma
authors: I
authors: Estrada
authors: Tsu-Shuen
authors: TS
authors: Tsao
authors: Antine E
authors: AE
authors: Stenbit
authors: Ellen B
authors: EB
authors: Katz
authors: Maureen J
authors: MJ
authors: Charron
mesh_terms: D052242:Adiponectin / Q000097:blood; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D064429:Fatty Acid Synthases / Q000235:genetics / Q000378:metabolism; D005260:Female; D051275:Glucose Transporter Type 4 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D046529:Microscopy, Electron, Transmission; D018656:Muscle Fibers, Fast-Twitch / Q000378:metabolism* / Q000648:ultrastructure; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000648:ultrastructure; D052243:Resistin / Q000097:blood; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D052242:Adiponectin; D001786:Blood Glucose; D051275:Glucose Transporter Type 4; D052243:Resistin; C495693:Slc2a4 protein, mouse; D064429:Fatty Acid Synthases