Glucose enhancement of insulin action: elevated glucose levels increase insulin stimulation of 2-deoxyglucose uptake in cultured human fibroblasts.

Insulin stimulation of 2-deoxyglucose uptake in cultured human skin fibroblasts has been 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-stimulation 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. These data demonstrate that extracellular glucose levels influence insulin action in cultured fibroblasts. This implies that insulin responsiveness in vivo may be regulated in some systems by ambient glucose levels.