A High-fructose Diet Impairs Akt and PKCζ Phosphorylation and GLUT4 Translocation in Rat Skeletal Muscle

Abstract

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 ζ (PKCζ), or glucose transporter 4 (GLUT4). However, insulin-stimulated phosphorylation of Akt and PKCζ 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 PKCζ activation and GLUT4 translocation in skeletal muscle.

Key words

insulin resistance - euglycemic clamp - protein kinase - glucose transporter - insulin signaling

References

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