Rapid Publication: Hyperglycemia Inhibits Insulin Activation of Akt/Protein Kinase B But Not Phosphatidylinositol 3-Kinase in Rat Skeletal Muscle

摘要

Sustained hyperglycemia impairs insulin-stimulated glucose utilization in the skeletal muscle of both humans and experimental animals-a phenomenon referred to clinically as glucose toxicity. To study how this occurs, a model was developed in which hypergly- cemia produces insulin resistance in vitro. Rat extensor digitorum longus mucles were preincubated for 4 h in Krebs-Henseleit solution containing glucose or glucose + insulin at various concentrations, after which insulin action was studied. Preincubation with 25 mmol/l glu- cose +insulin (10 mU/ml) led to a 70/100 decrease in the ability of insulin (10 mU/ml) to stimulate glucose incor- poration into glycogen and a 30/100 decrease in 2-deoxyglucose (2-DG) uptake, compared with muscles incubated with 0 mmol/l glucose.