EFFECTS OF INTERFERON ALPHA ON INSULIN BINDING AND GLUCOSE-TRANSPORT IN HUMAN ADIPOCYTES

We have previously demonstrated that interferon administration impairs glucose tolerance and causes insulin resistance in healthy man. Whether this is a direct effect of interferon is not known. The present study was undertaken to examine directly the effect of interferon alpha on insulin binding and action on glucose transport in isolated human adipocytes. Different concentrations of interferon alpha (range 10(-3)-10(5) IU ml-1) and different incubation times (0-5-24 h) with interferon were employed. Acute and 5-h and 24-h exposure of human adipocytes to 10(-2)-10 IU ml-1 of interferon increased the high affinity binding of I-125-insulin (P < 0.05). In contrast, human interferon alpha had no effect on insulin binding in rat adipocytes. In short-term studies interferon had no effect on C-14-glucose transport clearance. 24-h preincubation of human adipocytes with 10(-2), 10, 10(4) IU ml-1 interferon increased maximally-insulin stimulated C-14-glucose transport clearance (P < 0.05) and glucose transport responsiveness to insulin was enhanced by 24% (P < 0.05) in cells exposed to 10(-2) IU ml-1 interferon. After 5 and 24-h preincubations with interferon we observed modest changes in glucose transport sensitivity to moderate concentrations of insulin (50-100 pM) with upregulation in the presence of 10(-2)-10 IU ml-1 interferon and downregulation in the presence of 10(4)-10(5) IUm ml-1 interferon (P < 0.05). The insulin sensitivity index (ED50) did not change. These results indicate that human interferon alpha at low (10(-2)-10 IU ml-1) concentrations: (a) increases the high affinity binding of insulin to adipocytes; (b) this phenomenon is species specific. (c) after prolonged preincubations, interferon alpha may also modulate, in a complex way, the sensitivity and responsiveness of glucose transport system to insulin.