Insulin stimulation of glucose transport and metabolism in a human Wilms' tumor‐derived myoblast‐like cell Line: Modulation of hormone effects by glucose deprivation

The effects of insulin and glucose on parameters of metabolism were investigated in myoblast‐like (MBL) cells, a human myoblast‐like cell line derived from a Wilms' tumor. Insulin responses were studied after 4 hr pre‐incubation in serum free media, with or without 5 mM glucose. Insulin was added during the last 2 hr. Glucose starvation markedly increased basal glucose transport (measured as 2‐deoxyglucose uptake) as well as the net uptake of [¹⁴C]glucose and [¹⁴C]glucose incorporation into glycogen. Insulin stimulated net glucose uptake and incorporation into glycogen in a dose‐dependent manner in glucose‐fed and starved cells. These insulin responses were markedly enhanced in glucose‐starved cells. Insulin accelerated 2‐deoxyglucose transport in glucose‐fed cells but did not further stimulate basal glucose transport in glucose‐deprived cells. Insulin increased the incorporation of [³H]leucine into protein in glucose‐fed or ‐starved MBL cells equally. The dose of insulin required for half‐maximal insulin responses was similar for all parameters studied. Cycloheximide did not prevent the increased basal glucose incorporation in glucose‐starved cells, but markedly inhibited the insulin response, while in glucose‐fed cells, cycloheximide stimulated basal glucose incorporation. We conclude that MBL cells resemble fibroblasts in their insulin‐independent stimulation of glucose transport in response to glucose‐deprivation; when provided with glucose, they respond to insulin like fibroblasts. However, after brief glucose‐starvation, the stimulated glucose transport system is no longer insulin‐responsive in MBL cells, while pathways leading to the synthesis of macromolecules demonstrate preserved or enhanced stimulation by insulin, suggesting that these cells may serve as models to study the regulation of receptor‐response coupling by the metabolic milieu.