Abstract:
:Prolonged exposure to elevated glucocorticoid levels is known to produce insulin resistance (IR), a hallmark of diabetes mellitus. Although not fully elucidated, the underlying molecular mechanisms by which glucocorticoids induce IR may provide potential targets for pharmacological interventions. Here we characterized muscle lipid metabolism in a dexamethasone-aggravated diet-induced obesity murine model of IR. Male C57BL/6 mice on a high-fat diet for 2 months when challenged with dexamethasone showed elevated food consumption and weight gain relative to age and diet-matched animals dosed with saline only. Dexamethasone treatment impaired glucose tolerance and significantly increased the intramyocellular lipid content in the tibialis anterior muscle (TA). A good correlation (r = 0.76, P < 0.01) was found between accumulation in intramyocellular lipid content in the TA and visceral adiposity. The linoleic acid (18:2) to polyunsaturated acid ratio was increased in the dexamethasone-treated animals (+29%; P < 0.01), suggesting a possible increase in stearoyl-CoA desaturase 2 activity, as reported in Sertoli cells. The treatment was also accompanied by a reduction in the percent fraction of omega-3 and long-chain polyunsaturated fatty acids in the TA. Analysis of the low-molecular-weight metabolites from muscle extracts showed that there was no dysregulation of muscle amino acids, as has been associated with dexamethasone-induced muscle proteolysis. In conclusion, dexamethasone-induced insulin resistance in diet-induced obese mice is associated with a profound perturbation of lipid metabolism. This is particularly true in the muscle, in which an increased uptake of circulating lipids along with a conversion into diabetogenic lipids can be observed.
journal_name
Endocrinologyjournal_title
Endocrinologyauthors
Gounarides JS,Korach-André M,Killary K,Argentieri G,Turner O,Laurent Ddoi
10.1210/en.2007-1214subject
Has Abstractpub_date
2008-02-01 00:00:00pages
758-66issue
2eissn
0013-7227issn
1945-7170pii
en.2007-1214journal_volume
149pub_type
杂志文章相关文献
ENDOCRINOLOGY文献大全abstract::The aim of the present study was to investigate the presence and localization of the main G protein alpha-subunits in the human fetal adrenal gland during the second trimester of gestation. Immunofluorescence studies conducted on sections from frozen glands obtained immediately after therapeutic abortion indicated tha...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.141.12.7834
更新日期:2000-12-01 00:00:00
abstract::Recently, we have reported that retinoic acid (RA), similarly to retinol acetate, is able to reinitiate spermatogenesis in vitamin A-deficient rats. Here, we investigated the expression of RA receptors RAR alpha, RAR beta, RAR gamma, and retinoid X receptor RXR alpha by Northern blot analysis of poly(A)+ RNA of testes...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.131.1.1319320
更新日期:1992-07-01 00:00:00
abstract::Prolactin (PRL) shares several characteristics with growth factors and cytokines, many of which are known to bind to heparan sulfate proteoglycans. In this study we examined the heparin-binding properties of selected members of the PRL/GH family, using heparin affinity columns followed by gel electrophoresis/Western b...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.140.2.6677
更新日期:1999-02-01 00:00:00
abstract::The specific uptake by rat liver of human (hGH) and bovine (bGH) GHs labeled with 125I was studied by an in vivo procedure. A significant reduction of the uptake was observed when labeled hormones were injected together with different amounts of the corresponding native GH. This reduction was dose dependent, and the c...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-103-4-1190
更新日期:1978-10-01 00:00:00
abstract::The effects of estrogens, androgens, and glucocorticoids on bone resorption were compared in organ culture. At a concentration of 10(-5) M, corticosterone, testosterone, dihydrotestosterone, dehydroepiandosterone, estradiol, ethinyl estradiol and estrone did not inhibit the release of 45Ca from 19-day fetal rat long b...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-98-4-1065
更新日期:1976-04-01 00:00:00
abstract::The heart has epicardial adipose tissue that produces adipokines and mesenchymal stem cells. Systemic adipose tissue is involved in the pathophysiology of obesity-related heart diseases. However, the method for analyzing the direct interaction between adipose tissue and cardiomyocytes has not been established. Here we...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2010-1106
更新日期:2011-04-01 00:00:00
abstract::The development of acquired resistance to antihormonal agents in breast cancer is a major therapeutic problem. We have developed a tamoxifen-resistant (TAM-R) MCF-7 breast cancer cell line to investigate the mechanisms behind this condition. Both epidermal growth factor receptor (EGFR) and c-erbB2 mRNA and protein exp...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2002-220620
更新日期:2003-03-01 00:00:00
abstract::Nucleic acid-based therapies offer great potential for treatment of a variety of diseases including cancer by modulating protein expression with DNA or small interfering RNA. However, realization of their full therapeutic potential is currently limited due to an inability to reach the target site in an active form. Id...
journal_title:Endocrinology
pub_type: 杂志文章,评审
doi:10.1210/en.2009-1045
更新日期:2010-02-01 00:00:00
abstract::Hypothalamic insulin signaling is essential to the maintenance of glucose and energy homeostasis. During pathological states, such as obesity and type 2 diabetes mellitus, insulin signaling is impaired. One key mechanism involved in the development of insulin resistance is lipotoxicity, through increased circulating s...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2009-1122
更新日期:2010-02-01 00:00:00
abstract::We have recently demonstrated that 17beta-estradiol (E2) opposes cytokine-dependent increase of inducible nitric oxide synthase (iNOS) activity in rat smooth muscle cells and proposed that this effect might be associated to an antiinflammatory activity of this hormone. In the present study, we examine the E2 effects o...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.141.4.7404
更新日期:2000-04-01 00:00:00
abstract::Prolonged exposure to elevated FFA levels has been shown to induce peripheral insulin resistance and to alter the beta-cell secretory response to glucose. To investigate the effects of FFAs on preproinsulin gene expression, we measured insulin release, cell content, and messenger RNA (mRNA) levels in rat islets after ...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.140.9.6953
更新日期:1999-09-01 00:00:00
abstract::This study investigates the signaling pathways that lead to acute augmentation of secretagogue-induced LH secretion, the physiologically relevant manifestation of which is LHRH self-potentiation. The consequence of LHRH self-potentiation is an augmented LH secretory response to subsequent exposure to the peptide. Alth...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.130.6.1317780
更新日期:1992-06-01 00:00:00
abstract::Mast cells are involved in atopic disorders, often exacerbated by stress, and are located perivascularly close to sympathetic and sensory nerve endings. Mast cells are activated by electrical nerve stimulation and millimolar concentrations of neuropeptides, such as substance P (SP). Moreover, acute psychological stres...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.139.1.5660
更新日期:1998-01-01 00:00:00
abstract::Adult rats which have received monosodium-L-glutamate (MSG, 4 mg/g BW) on alternate days for the first 10 days of life manifest central nervous system lesions largely restricted to the retina and the arcuate nucleus of the hypothalamus in which nearly 90% of the perikarya are destroyed, leaving axons in passage intact...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-103-1-170
更新日期:1978-07-01 00:00:00
abstract::In several mammalian species, luteinizing hormone-releasing hormone (LHRH) neurons have been shown to migrate from nasal regions to the brain during early development. Using immunocytochemistry, we have identified LHRH containing neurons in developing chick embryos. In embryonic day 4 (E4) and E5 animals, a small grou...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-128-3-1676
更新日期:1991-03-01 00:00:00
abstract::Estrogen inhibits postmenopausal bone loss and decreases fracture risk. Unfortunately, estrogen replacement therapy has many undesirable side effects, the majority of which are due to stimulation of reproductive tissues. Tissue specific estrogen agonists provide a promising new alternative to natural estrogens for hor...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.138.5.5109
更新日期:1997-05-01 00:00:00
abstract::Many New World primate species have elevated circulating free plasma cortisol concentrations, target tissue resistance to cortisol, and no evidence of sodium retention. A representative New World primate, the squirrel monkey (Saimiri sciureus), has plasma cortisol concentrations above those necessary to cause complete...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-115-1-25
更新日期:1984-07-01 00:00:00
abstract::GH controls its own secretion through a mechanism involving short-loop feedback regulation of the synthesis and release of GH-releasing hormone (GHRH). GHRH neurons coexpress the peptide galanin, but the functional significance of this coexpression is unknown. In this study, we tested the hypotheses that 1) galanin ge...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.137.12.8940350
更新日期:1996-12-01 00:00:00
abstract::Orexins/hypocretins heavily innervate the posterior division of the paraventricular nucleus of the thalamus (pPVT), which expresses both orexin receptor types. The pPVT is important for adaptations to repeated stress, particularly the ability to facilitate to novel stress after repeated stress exposure. Here, we exami...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2011-1652
更新日期:2011-12-01 00:00:00
abstract::The increase in glucagon-like peptide-1 (GLP-1) activity has emerged as a useful therapeutic tool for the treatment of type 2 diabetes mellitus. The actions of GLP-1 on β-cells and the nervous and digestive systems are well known. The action of this peptide in adipose tissue (AT), however, is still poorly defined. Fur...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2011-1070
更新日期:2011-11-01 00:00:00
abstract::Frequent blood sampling via intraatrial cannula revealed daily rhythms of TSH and thyroid hormones in both male and female Wistar rats. Thermic ablation of the biological clock, i.e. the suprachiasmatic nucleus (SCN), eliminated the diurnal peak in circulating TSH and thyroid hormones. In addition, SCN lesions produce...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.141.10.7709
更新日期:2000-10-01 00:00:00
abstract::Corticosteroids stimulate and insulin inhibits energy acquisition (food intake); conversely, corticosteroids inhibit and insulin stimulates energy storage (body weight gain). Thus, together these hormones mediate long-term energy balance. This study tested whether the stimulatory action of corticosteroids on food inta...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.136.5.7720670
更新日期:1995-05-01 00:00:00
abstract::Estrogen deficiency induced by menopause leads to an increase in bone resorption that is not compensated for by a comparable increase in bone formation, resulting in excessive bone loss. Clinically, estrogen replacement reverses these processes, but the mechanisms by which this takes place are not completely understoo...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.137.2.8593810
更新日期:1996-02-01 00:00:00
abstract::We have developed a highly sensitive and specific RIA for propylthiouracil (PTU) which uses 125I-labeled PTU as the radioactive ligand. At a final antibody dilution of 1:10,000, the detection limit for PTU was 100 pg; cross-reactivity with circulating, urinary, and intrathyroid PTU metabolites was negligible. Using th...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-113-3-915
更新日期:1983-09-01 00:00:00
abstract::We hypothesized the existence of vagal arginine sensors in the liver which modulate arginine-induced pancreatic hormone secretion. The present study was carried out to examine the efferent pathways and receptor mechanisms from arginine sensors using selective vagotomies and autonomic drugs on the secretion of insulin ...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-127-4-2017
更新日期:1990-10-01 00:00:00
abstract::Tumor necrosis factor-alpha (TNF) and interleukin-1 beta (IL-1) are secreted by activated monocytes and other immune cells. Since IL-1 has been shown to elevate rat plasma ACTH and both of these cytokines induce similar acute-phase responses, the present studies of TNF were undertaken to characterize the ACTH response...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-124-6-3131
更新日期:1989-06-01 00:00:00
abstract::Equine CG (eCG) both radioiodinated and unlabeled, was injected iv into male rats, and the disappearance of the hormone from the circulation was studied. The uptake and inactivation of the hormone by various tissues was also examined. The disappearance curve of eCG consisted of two exponential components with apparent...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-109-4-1242
更新日期:1981-10-01 00:00:00
abstract::Four different GnRHs and one GnRH receptor are reported to be expressed in various mammals, whereas 13 GnRHs and numerous GnRH receptors have been identified in various nonmammalian vertebrates. The nucleotide sequencing of the human genome provided the opportunity to determine which of these peptides and receptors mi...
journal_title:Endocrinology
pub_type: 杂志文章,评审
doi:10.1210/endo.143.3.8705
更新日期:2002-03-01 00:00:00
abstract::Interleukin-6 (IL-6) stimulates the release of hCG from syncytiotrophoblast cells, but the effects of IL-6 and other cytokines on the release of placental lactogen (hPL) are unknown. To determine the effect of IL-6 on hPL release, we exposed an enriched fraction of trophoblast cells (prepared by the isopycnic centrifu...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.135.2.8033820
更新日期:1994-08-01 00:00:00
abstract::Pharmacological amounts of 25(s),26-dihydroxyvitamin D3 were administered to normal, vitamin D-replete rats in order to assess its pharmacological activity. Treatment with 25(s),26-dihydroxyvitamin D3 (20 micrograms/day for 1 week) caused a marked and significant fall in the circulating concentration of 1,25-dihydroxy...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-121-5-1671
更新日期:1987-11-01 00:00:00