Abstract:
OBJECTIVE:Glucocorticoid excess leads to insulin resistance. This study explores the effects of glucocorticoids on the glucose transport system and insulin signalling in rat adipocytes. The interaction between glucocorticoids and high levels of insulin and glucose is also addressed. DESIGN AND METHODS:Isolated rat adipocytes were cultured for 24 h at different glucose concentrations (5 and 15 mmol/l) with or without the glucocorticoid analogue dexamethasone (0.3 micromol/l) and insulin (10(4) microU/ml). After the culture period, the cells were washed and then basal and insulin-stimulated glucose uptake, insulin binding and lipolysis as well as cellular content of insulin signalling proteins (insulin receptor substrate-1 (IRS-1), IRS-2, phosphatidylinositol 3-kinase (PI3-K) and protein kinase B (PKB)) and glucose transporter isoform GLUT4 were measured. RESULTS:Dexamethasone in the medium markedly decreased both basal and insulin-stimulated glucose uptake at both 5 and 15 mmol/l glucose (by approximately 40-50%, P<0.001 and P<0.05 respectively). Combined long-term treatment with insulin and dexamethasone exerted additive effects in decreasing basal, and to a lesser extent insulin-stimulated, glucose uptake capacity (P<0.05) compared with dexamethasone alone, but this was seen only at high glucose (15 mmol/l). Insulin binding was decreased (by approximately 40%, P<0.05) in dexamethasone-treated cells independently of surrounding glucose concentration. Following dexamethasone treatment a approximately 75% decrease (P<0.001) in IRS-1 expression and an increase in IRS-2 (by approximately 150%, P<0.001) was shown. Dexamethasone also induced a subtle decrease in PI3-K (by approximately 20%, P<0.01) and a substantial decrease in PKB content (by approximately 45%, P<0.001). Insulin-stimulated PKB phosphorylation was decreased (by approximately 40%, P<0.01) in dexamethasone-treated cells. Dexamethasone did not alter the amount of total cellular membrane-associated GLUT4 protein. The effects of dexamethasone per se on glucose transport and insulin signalling proteins were mainly unaffected by the surrounding glucose and insulin levels. Dexamethasone increased the basal lipolytic rate (approximately 4-fold, P<0.05), but did not alter the antilipolytic effect of insulin. CONCLUSIONS:These results suggest that glucocorticoids, independently of the surrounding glucose and insulin concentration, impair glucose transport capacity in fat cells. This is not due to alterations in GLUT4 abundance. Instead dexamethasone-induced insulin resistance may be mediated via reduced cellular content of IRS-1 and PKB accompanied by a parallel reduction in insulin-stimulated activation of PKB.
journal_name
Eur J Endocrinoljournal_title
European journal of endocrinologyauthors
Burén J,Liu HX,Jensen J,Eriksson JWdoi
10.1530/eje.0.1460419subject
Has Abstractpub_date
2002-03-01 00:00:00pages
419-29issue
3eissn
0804-4643issn
1479-683Xpii
146419journal_volume
146pub_type
杂志文章abstract:BACKGROUND AND OBJECTIVES:Primary hyperparathyroidism (PHPT) is associated with increased cardiovascular mortality and morbidity. Little is known about hemostatic features of patients with PHPT. To our knowledge, plasma tissue factor pathway inhibitor (TFPI) and thrombin-activatable fibrinolysis inhibitor (TAFI) levels...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/EJE-09-0069
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journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/EJE-10-0397
更新日期:2010-07-01 00:00:00
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abstract:Objective:Pancreatic neuroendocrine neoplasms (PanNENs) are rare tumors arising from the endocrine pancreas; however, their prognosis differs significantly upon their proliferative state, which is characterized by histopathological grading. MiRNAs are small, noncoding RNAs posttranscriptionally regulating gene expressi...
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journal_title:European journal of endocrinology
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journal_title:European journal of endocrinology
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abstract:BACKGROUND:Fetal growth restriction (FGR) has been related to several health risks, which have been generally identified in small-for-gestational age (SGA) individuals. OBJECTIVE:To evaluate the impact of FGR on body composition and hormonal status in infants born either small- or appropriate-for-gestational age (AGA)...
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abstract::Giant prolactinomas are rare tumours, representing only 2-3% of all prolactin (PRL)-secreting tumours and raising special diagnostic and therapeutic challenges. Based on several considerations developed in this review, their definition should be restricted to pituitary adenomas with a diameter of 40 mm or more, signi...
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更新日期:2011-12-01 00:00:00
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更新日期:1996-09-01 00:00:00
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journal_title:European journal of endocrinology
pub_type: 杂志文章
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journal_title:European journal of endocrinology
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journal_title:European journal of endocrinology
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doi:10.1530/eje.0.1480597
更新日期:2003-06-01 00:00:00
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journal_title:European journal of endocrinology
pub_type: 杂志文章,评审
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更新日期:2012-02-01 00:00:00
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journal_title:European journal of endocrinology
pub_type: 杂志文章
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journal_title:European journal of endocrinology
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更新日期:2001-07-01 00:00:00
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更新日期:2004-10-01 00:00:00
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journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/eje.0.1370701
更新日期:1997-12-01 00:00:00
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journal_title:European journal of endocrinology
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更新日期:2021-02-01 00:00:00
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journal_title:European journal of endocrinology
pub_type: 杂志文章
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更新日期:1996-07-01 00:00:00
abstract::The recent onslaught of mass spectrometry (MS) to measurements of steroid hormones, including demands that they should be the only acceptable method, has confused clinicians and scientists who have relied for more than 40 years on a variety of immunoassay (IA) methods in steroid hormone measurements. There is little d...
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pub_type: 杂志文章,评审
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更新日期:2015-08-01 00:00:00
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journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/EJE-14-0864
更新日期:2015-04-01 00:00:00
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journal_title:European journal of endocrinology
pub_type: 杂志文章,评审
doi:10.1530/eje.0.1440319
更新日期:2001-04-01 00:00:00
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journal_title:European journal of endocrinology
pub_type: 杂志文章
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更新日期:2008-05-01 00:00:00
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pub_type: 杂志文章,随机对照试验
doi:10.1530/EJE-07-0857
更新日期:2008-06-01 00:00:00