Carbohydrate inhibitors of concanavalin A that inhibit binding of insulin-sepharose to fat cells and antagonize and mimic insulin's bioactivity. A possible role for membrane carbohydrate in insulin's action.

A consistent pattern of insulin-like properties is expressed by a variety of glycoside inhibitors of concanavalin A (Con A), and is suggestive of a common mechanism of action to explain these effects. Various exogenously added glycoside derivatives inhibit the binding of insulin-Sepharose beads to insulin receptors on isolated intact rat fat cells with a specificity resembling that for Con A-Sepharose binding to these cells. A more limited number of glycosides tested were also found to inhibit the binding of 125I-insulin, although some enhancement of binding that preceded the inhibition was observed for some of these saccharides. The glycosides also antagonize insulin-stimulated glucose utilization by the cells, but in some cases also mimic the hormone by stimulating glucose utilization. A few glycosides mimic insulin without appearing to antagonize its bioactivity. Radiolabeled glycoside inhibitors fail to bind to insulin in equilibrium dialysis experiments although they readily bind to Con A, indicating that the glycosides act directly on the cell rather than on the insulin molecule. The latter observation is consistent with the ability of those glycosides that act like insulin to do so independent of the hormone. In view of the known insulin-like properties of Con A, the effects of the glycosides seen in the present study suggest roles for a membrane carbohydrate and a carbohydrate binding site in the mechanisms of action of both insulin and Con A. In addition to various alternative explanations, a working hypothesis is presented to rationalize the present observations. It proposes that the effects of the exogenously added glycosides (and Con A) may reflect the presence on the membrane of a native carbohydrate moiety by either mimicking or competitively inhibiting its ability to interact reversibly with a lectin-like carbohydrate binding site associated with the function of the insulin receptor.20