A high-fructose diet impairs Akt and PKCzeta phosphorylation and GLUT4 translocation in rat skeletal muscle.
The molecular mechanism of insulin resistance induced by high-fructose feeding is not fully understood. The present study investigated the role of downstream signaling molecules of phosphatidylinositol 3-kinase (PI3K) in the insulin-stimulated skeletal muscle of high-fructose-fed rats. Rats were divided into chow-fed and fructose-fed groups. The results of the euglycemic clamp study (insulin infusion rates: 6 mU/kg BW/min) showed a significant decrease in the glucose infusion rate (GIR) and the metabolic clearance rate of glucose (MCR) in fructose-fed rats compared with chow-fed rats. In skeletal muscle removed immediately after the clamp procedure, high-fructose feeding did not alter protein levels of protein kinase B (PKB/Akt), protein kinase C zeta (PKCzeta), or glucose transporter 4 (GLUT4). However, insulin-stimulated phosphorylation of Akt and PKCzeta and GLUT4 translocation to the plasma membrane were reduced. Our findings suggest that insulin resistance in fructose-fed rats is associated with impaired Akt and PKCzeta activation and GLUT4 translocation in skeletal muscle.
Li
P
P
Department of Sports Medicine, Graduate School of Medicine, Nagoya University, Nagoya, Japan.
Koike
T
T
Qin
B
B
Kubota
M
M
Kawata
Y
Y
Jia
Y J
YJ
Oshida
Y
Y
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D015153:Blotting, Western; D004032:Diet / Q000009:adverse effects*; D005632:Fructose / Q000009:adverse effects*; D015309:Glucose Clamp Technique; D051275:Glucose Transporter Type 4 / Q000378:metabolism*; D007328:Insulin / Q000502:physiology; D008297:Male; D018482:Muscle, Skeletal / Q000201:enzymology / Q000378:metabolism; D051058:Oncogene Protein v-akt / Q000378:metabolism*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*; D021381:Protein Transport / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D000099221:Protein Kinase C zeta
D001786:Blood Glucose; D005632:Fructose; D051275:Glucose Transporter Type 4; D007328:Insulin; D051058:Oncogene Protein v-akt; D011493:Protein Kinase C; D000099221:Protein Kinase C zeta; C495694:Slc2a4 protein, rat