Insulin receptor and altered glucose transport in a monensin‐resistant mutant of Chinese hamster ovary cell

A monensin‐resistant mutant Mon^r‐31, derived from Chinese hamster ovary (CHO) cell line, has been shown to have a reduced number of insulin receptors and a reduction in glucose uptake in response to insulin. We have further investigated the possibility that altered glucose uptake in Mon^r‐31 cells is related to an alteration in the activity of the insulin receptor. Uptake of glucosamine, 2‐deoxy‐D‐glucose, and 3‐O‐methyl‐D‐glucose in Mon^r‐31 cells was one‐half to one‐third that of CHO cells. The cellular content of the glucose transporter in Mon^r‐31 was reduced to about one‐third that of CHO as assayed by use of an antiglucose transporter antibody. After transfection with the human insulin receptor cDNA, we obtained clones CIR‐0 from CHO, and MIR‐2 and MIR‐15 from Mon^r‐31; CIR‐0 expressed a tenfold higher level of the insulin‐binding activity than did CHO, and MIR‐2 and MIR‐15 expressed a 20‐fold higher level than did Mon^r‐31. Glucose uptake in both CHO and CIR‐0 was significantly enhanced by exogenous insulin, but not in Mon^r‐31, MIR‐2, and MIR‐15. The β‐subunits of insulin receptor in CHO, CIR‐0, Mon^r‐31, and MIR‐2 were similarly phosphorylated. The decreased glucose transport activity in Mon^r‐31 cells is discussed in relation to the absence or presence of insulin receptor expression.