Glucose Enhancement of Insulin Action: Elevated Glucose Levels Increase Insulin Stimulation of 2-Deoxyglucose Uptake in Cultured Human Fibroblasts*

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Abstract
Insulin stimulation of 2-deoxyglucose uptake in cultured human skin fibroblasts was examined in the presence of varying concentrations of extracellular glucose. When cell monolayers were preincubated in glucose-free medium, insulin stimulation of hexose transport was small. Increasing glucose levels from 2.7 to 16.7 mM in the preincubation medium enhanced insulin-stimulated 2-deoxyglucose uptake (18-65% of basal uptake). Insulin stimulation of hexose transport in the presence of glucose was the result of an increase in the Vmax without a significant change in the Km of transport. Maximum enhancement of insulin action was achieved 18-24 h after glucose exposure. After 24 h, the insulin response decreased. Glucose did not influence the concentration of insulin required for half-maximal stimulation. Growth conditions also altered the magnitude of insulin stimulation of 2-deoxyglucose uptake; the response was maximal in confluent cells (5-10 days of culture) and decreased during senescence. Extracellular glucose levels influence insulin action in culture fibroblasts. Insulin responsiveness in vivo may be regulated in some systems by ambient glucose levels.