Effects of cyclic AMP elevation on the levels of insulin receptors in glial C6 cells.
The regulation of the insulin receptor by cAMP has been examined in glial C6 cells. Incubation for 48 h with dibutyryl cyclic AMP produced a dose-dependent inhibition of 125I-insulin binding to the cells. Other agents that elevate intracellular cAMP levels such as forskolin and cholera toxin mimicked the effect of this cyclic AMP analog. With all compounds the maximal decrease of binding was found between 24 and 48 h and normally varied between 40 and 60%. Forskolin, cholera toxin and dibutyryl cyclic AMP also affected C6 cell proliferation, and the dose-response for decreasing the receptor was very similar to that observed for the inhibition of cell growth, suggesting a relationship between both phenomena. Scatchard analysis showed that cAMP did not produce major changes in the affinity of the receptor for insulin, but rather decreased receptor number. An accumulation of receptors at the cell surface was observed in the absence of de novo protein synthesis, since cycloheximide caused a significant increase in insulin binding to the cells. This inhibitor almost totally blocked the cAMP effect both when added simultaneously to the cells with the agents which increase cAMP and when added to cells pre-treated for 48 h with the same compounds.
Montiel
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Unidad de Endocrinologia Experimental, C.S.I.C., Facultad de Medicina, Universidad Autonoma de Madrid, Spain.
Aranda
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Pascual
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D000818:Animals; D003994:Bucladesine / Q000494:pharmacology*; D002460:Cell Line; D002772:Cholera Toxin / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D003513:Cycloheximide / Q000494:pharmacology; D005910:Glioma / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D051381:Rats; D011972:Receptor, Insulin / Q000187:drug effects* / Q000378:metabolism
D007328:Insulin; D005576:Colforsin; D003994:Bucladesine; D002772:Cholera Toxin; D003513:Cycloheximide; D000242:Cyclic AMP; D011972:Receptor, Insulin