Transcriptional repression of the mouse insulin-responsive glucose transporter (GLUT4) gene by cAMP
Autor: | J R Flores-Riveros, M Janicot, M D Lane, J C McLenithan, Klaus H. Kaestner |
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Rok vydání: | 1991 |
Předmět: |
Basal rate
medicine.medical_specialty Monosaccharide Transport Proteins Transcription Genetic Glucose uptake Adipose tissue 8-Bromo Cyclic Adenosine Monophosphate Deoxyglucose Cell Line chemistry.chemical_compound Mice Adipocyte Internal medicine medicine Cyclic AMP Animals Cell Nucleus Multidisciplinary biology Colforsin Glucose transporter Isoproterenol nutritional and metabolic diseases MRNA stabilization Glucagon Kinetics Endocrinology Antisense Elements (Genetics) chemistry Adipose Tissue biology.protein RNA GLUT1 GLUT4 hormones hormone substitutes and hormone antagonists Research Article |
Zdroj: | Proceedings of the National Academy of Sciences of the United States of America. 88(5) |
ISSN: | 0027-8424 |
Popis: | Glucose uptake by adipose tissue is mediated by two glucose transporters: GLUT4, which is most abundant, and GLUT1. While GLUT1 is expressed in many tissues, GLUT4 is unique to tissues that exhibit insulin-stimulated glucose uptake (heart and skeletal muscle and adipose tissue). In the diabetic state and during starvation, insulin-stimulated glucose uptake and GLUT4 expression are decreased in tissue adipocytes. Using 3T3-L1 adipocytes in culture, we investigated the possibility that these effects are mediated by elevated cellular cAMP. When 3T3-L1 adipocytes were treated for 16 hr with forskolin or 8-Br-cAMP, GLUT4 mRNA and protein were decreased by approximately 70%, while expression of GLUT1 mRNA and protein was increased 3-fold. These changes were accompanied by an increased basal rate of 2-deoxyglucose uptake and a loss of acute responsiveness of hexose uptake to insulin. The magnitude of GLUT4 mRNA depletion/GLUT1 mRNA accumulation was dependent upon the concentration of 8-Br-cAMP. The decrease of GLUT4 mRNA caused by 8-Br-cAMP was the result of a decreased transcription rate, while the half-life of the message was unaffected. The increase in GLUT1 mRNA caused by 8-Br-cAMP was the result of both transient transcriptional activation and mRNA stabilization. We suggest that down-regulation of GLUT4 mRNA in adipose tissue in the diabetic state and during starvation is the result of repression of transcription of the GLUT4 gene caused by cAMP. |
Databáze: | OpenAIRE |
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