Objective: To discusse the molecular mechanisms of impaired glucose tolerance(IGT) development induced by long term high-fat diet by investigating the protein expressions of phosphatidyl inositol 3-kinase (PI3K)/protein kinase B (PKB)/glycogen synthase kinase-3β (GSK-3β)/glucose transporter-4 (GLUT-4) in the rat skeletal muscle with IGT. Method: The IGT rat model was replicated by being fed with high fat diet with 45% lipid energy for twenty weeks. The protein concentration of PI3K in the skeletal muscle was examined by immunohistochemical staining

the protein expressions of PKB/GSK-3β/GLUT-4 were detected by Western Blot

and the relative amount of GLUT-4 protein in IGT rats skeletal muscle tissue was tested by Real Time-PCR. Result: Compared to the control group

the protein expressions of PI3K/PKB in skeletal muscle of IGT group were all decreased

the protein expressions of GSK-3β was obvously increased (P<0.01). The mRNA expression of GLUT-4 in IGT group was decreased as compared with the control group

but there was no significant difference. Conclusion: The protein expressions of PKB/GSK-3β/GLUT-4 in skeletal muscle of IGT rats established by long-term high fat diet with 45% lipid energy are obviously changed

which seems to be one of the molecular mechanisms for IGT in this model formation.