Regulation of human insulin receptor RNA splicing in HepG2 cells: effects of glucocorticoid and low glucose concentration.
Human insulin receptor RNA is expressed in two alternatively spliced forms (Ex. 11- and Ex. 11+) encoding protein isoforms with discrete functional differences. In vivo, the splicing varies between tissues and changes concomitantly with the control of glucose homeostasis. Recently, dexamethasone has been described to increase the relative expression of Ex. 11+ RNA molecules. In this study, we confirm that dexamethasone dose-dependently increases inclusion of exon 11, and demonstrate that low concentrations of glucose decrease inclusion. No effect was observed of either insulin or IGF1. These results suggest that hormonal as well as metabolic factors regulate the splicing of insulin receptor RNA in HepG2 cells.
Norgren
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Rolf Luft Center for Diabetes Research, Department of Clinical Genetics, Karolinska Hospital, Stockholm, Sweden.
Li
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LS
Luthman
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H
D017398:Alternative Splicing / Q000187:drug effects*; D006528:Carcinoma, Hepatocellular; D003907:Dexamethasone / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D011972:Receptor, Insulin / Q000235:genetics*; D014407:Tumor Cells, Cultured
D007328:Insulin; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D003907:Dexamethasone; D011972:Receptor, Insulin; D005947:Glucose