Globular adiponectin increases GLUT4 translocation and glucose uptake but reduces glycogen synthesis in rat skeletal muscle cells.
OBJECTIVE
The aim of this study was to determine whether adiponectin elicits glucose uptake via increased GLUT4 translocation and to investigate the metabolic fate of glucose in skeletal muscle cells treated with globular adiponectin.


METHODS
Basal and insulin-stimulated 2-deoxy-D: -[(3)H]glucose uptake, cell surface myc-tagged GLUT4 content, production of (14)CO(2) by oxidation of D: -[U-(14)C]glucose and [1-(14)C]oleate, and incorporation of D: -[U-(14)C]glucose into glycogen and lactate were measured in the presence and absence of globular adiponectin.


RESULTS
RT-PCR and Western blot analysis revealed that L6 cells and rat skeletal muscle cells express AdipoR1 mRNA and protein. Globular adiponectin increased both GLUT4 translocation and glucose uptake by increasing the transport V(max) of glucose without altering the K(m). Interestingly, the incorporation of D: -[U-(14)C]glucose into glycogen under basal and insulin-stimulated conditions was significantly decreased by globular adiponectin, whereas lactate production was increased. Furthermore, globular adiponectin did not affect glucose oxidation, but enhanced phosphorylation of AMP kinase and acetyl-CoA carboxylase, and fatty acid oxidation.


CONCLUSIONS
The present study is the first to show that globular adiponectin increases glucose uptake in skeletal muscle cells via GLUT4 translocation and subsequently reduces the rate of glycogen synthesis and shifts glucose metabolism toward lactate production. These effects are consistent with the increased phosphorylation of AMP kinase and acetyl-CoA carboxylase and oxidation of fatty acids induced by globular adiponectin.
Ceddia
R B
RB
Department of Biology, York University, Toronto, ON, M3J 1P3, Canada.
Somwar
R
R
Maida
A
A
Fang
X
X
Bikopoulos
G
G
Sweeney
G
G
D000263:Adenylate Kinase / Q000378:metabolism; D052242:Adiponectin; D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D005947:Glucose / Q000378:metabolism; D051275:Glucose Transporter Type 4; D006003:Glycogen / Q000096:biosynthesis*; D007328:Insulin / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology*; D007773:Lactates / Q000378:metabolism; D009004:Monosaccharide Transport Proteins / Q000378:metabolism*; D009124:Muscle Proteins / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D019301:Oleic Acid / Q000378:metabolism; D021381:Protein Transport; D051381:Rats; D054419:Receptors, Adiponectin; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
C475418:ADIPOR1 protein, human; D052242:Adiponectin; D051275:Glucose Transporter Type 4; D007328:Insulin; D036341:Intercellular Signaling Peptides and Proteins; D007773:Lactates; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D054419:Receptors, Adiponectin; D011956:Receptors, Cell Surface; C495694:Slc2a4 protein, rat; D019301:Oleic Acid; D006003:Glycogen; D000263:Adenylate Kinase; D005947:Glucose