論文 - 詳細
| RRC ID | 43289 |
|---|---|
| 著者 | Iwasaki Y, Takayasu S, Nishiyama M, Tsugita M, Taguchi T, Asai M, Yoshida M, Kambayashi M, Hashimoto K. |
| タイトル | Is the metabolic syndrome an intracellular Cushing state? Effects of multiple humoral factors on the transcriptional activity of the hepatic glucocorticoid-activating enzyme (11beta-hydroxysteroid dehydrogenase type 1) gene. |
| ジャーナル | Mol Cell Endocrinol |
| Abstract |
Although glucocorticoid, as "gluco-" literally implies, plays an important role in maintaining the blood glucose level, excess of glucocorticoid production/action is known to cause impaired glucose tolerance and diabetes. Since 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1), which converts inactive cortisone to active cortisol, is primarily expressed in the liver, an enhanced expression of the enzyme may increase the intracellular glucocorticoid level and thus increase the hepatic glucose production. In this study, we examined the effects of multiple humoral factors related to the metabolic syndrome on the transcriptional activity of 11beta-HSD1 gene in hepatocytes in vitro. We found that, among the factors examined, adipocyte-derived cytokines (adipokines), like TNFalpha and IL-1beta, potently stimulated the transcriptional activity of 11beta-HSD1 gene in human HuH7 cells. In contrast, only minimal effects of other humoral factors were observed when they were used alone. Interestingly, however, when applied in combination, they synergistically enhanced the transcriptional activity of 11beta-HSD1 gene. They also potentiated the effects of cytokines. Glucocorticoid receptor (GR)-dependent transcription was indeed increased even with an inactive glucocorticoid cortisone following TNFalpha pretreatment, indicating the enhanced intracellular conversion. Finally, PPARgamma/PPARalpha agonists, clinically used as anti-diabetic drugs, significantly inhibited the transcriptional activity of 11beta-HSD1. Altogether, our data strongly suggest that combination of the humoral factors related to the metabolic syndrome, including the adipokines, synergistically enhances the hepatic expression of 11beta-HSD1 gene and causes the intracellular Cushing state in the liver by increasing the intracellular glucocorticoid level. We assume that the observed synergistic effects of these factors on 11beta-HSD1 may, at least partly, explain the reason whereby accumulation of the multiple risk factors facilitates the derangement of glucose and lipid metabolism in the metabolic syndrome. |
| 巻・号 | 285(1-2) |
| ページ | 10-8 |
| 公開日 | 2008-3-26 |
| DOI | 10.1016/j.mce.2008.01.012 |
| PII | S0303-7207(08)00006-3 |
| PMID | 18313835 |
| MeSH | 11-beta-Hydroxysteroid Dehydrogenase Type 1* / genetics 11-beta-Hydroxysteroid Dehydrogenase Type 1* / metabolism Animals Anticholesteremic Agents / metabolism Base Sequence Cell Line Chromans / metabolism Clofibrate / metabolism Cortisone / metabolism Cushing Syndrome / blood* Cushing Syndrome / enzymology* Cushing Syndrome / physiopathology Dexamethasone / metabolism Gene Expression Regulation, Enzymologic* Glucocorticoids / metabolism Humans Hydrocortisone / metabolism Hypoglycemic Agents / metabolism Insulin / metabolism Interleukin-1beta / metabolism Liver / metabolism Metabolic Syndrome / blood* Metabolic Syndrome / enzymology* Metabolic Syndrome / physiopathology Metformin / metabolism Molecular Sequence Data Receptors, Glucocorticoid / genetics Receptors, Glucocorticoid / metabolism Thiazolidinediones / metabolism Transcription Factor AP-1 / metabolism Troglitazone Tumor Necrosis Factor-alpha / metabolism |
| IF | 3.871 |
| 引用数 | 38 |
| WOS 分野 | ENDOCRINOLOGY & METABOLISM CELL BIOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 4 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | HuH-7(RCB1366) |