Virus-induced decrease of insulin receptors in cultured human cells.
Viral infections may produce abnormalities in carbohydrate metabolism in normal subjects and profound changes in glucose homeostasis in insulin-dependent diabetics. Using an in vitro radio-receptor assay with 125I-labeled insulin and human-amnion (WISH) cells, the effect of viral infections on insulin receptors was examined. Both herpes simplex virus and vesicular stomatitis virus produced a 50% decrease in insulin binding. There was no evidence that this decrease was due to degradation of insulin. On quantitative analysis, this decrease in binding was found to be the result of a decrease in receptor concentration with no change in receptor affinity. The decrease in receptors occurred between 4 and 12 h, at the time viral antigens were being inserted into the plasma membrane of infected cells. Because the t 1/2 of insulin receptors in uninfected cells was between 14 and 24 h, the decrease in insulin receptors cannot be explained solely by virus-induced shut-off of macromolecular synthesis. Moreover, viruses such as encephalomyocarditis that do not insert new antigens into the plasma membrane, did not cause changes in the number of insulin receptors. The most likely explanation is that virus-induced changes in the plasma membrane altered or displaced insulin receptors. It is concluded that the insulin receptor assay is a sensitive and quantitative method for studying the effect of viral infections on cell membranes. These data also suggest that abnormalities in glucose metabolism associated with some viral infections may be due, in part, to changes in the concentration of insulin receptors.
D000650:Amnion; D001665:Binding Sites / Q000187:drug effects; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D008459:Measles virus; D011691:Puromycin / Q000494:pharmacology; D011972:Receptor, Insulin / Q000502:physiology*; D018139:Simplexvirus; D014721:Vesicular stomatitis Indiana virus
D007328:Insulin; D011691:Puromycin; D003513:Cycloheximide; D011972:Receptor, Insulin