Abstract:
:Insulin receptor substrate-1 (IRS-1), the primary substrate for the insulin receptor tyrosine kinase in most cells and tissues, is a key component of the insulin signaling network. Numerous studies have documented the trafficking of IRS-1 from the cell membrane to intracellular, extranuclear compartments. During the course of our previous studies aimed at defining the ontogeny of insulin signaling in the rat, Western immunoblotting showed minimal IRS-1 content in late gestation fetal liver. Immunohistochemical analyses, aimed at corroborating these Western immunoblotting results, showed hepatocyte nuclear staining for IRS-1 in adult liver but not fetal liver. Further analysis of fixed tissue as well as immunofluorescent staining of liver cryosections confirmed the localization of IRS-1 to the nuclear matrix and nucleoli of adult hepatocytes within intact liver. Tissue fractionation and Western immunoblotting also showed nuclear localization of IRS-1, with this fraction accounting for approximately 25% of total liver IRS-1. Administration of insulin to intact animals did not stimulate nuclear translocation of hepatic IRS-1 or the p85 regulatory subunit of phosphatidylinositol-3 kinase. However, insulin did activate IRS-1-associated phosphatidylinositol-3 kinase in nuclear extracts. Our results indicate that insulin signaling, which terminates in an array of nuclear events, may originate at the immediate postreceptor level with IRS-1 activation within the nucleus of normal hepatocytes.
journal_name
Endocrinologyjournal_title
Endocrinologyauthors
Boylan JM,Gruppuso PAdoi
10.1210/en.2002-220321subject
Has Abstractpub_date
2002-11-01 00:00:00pages
4178-83issue
11eissn
0013-7227issn
1945-7170journal_volume
143pub_type
杂志文章相关文献
ENDOCRINOLOGY文献大全abstract::Endocrine regulation of uterine biology is critical for embryo receptivity and human reproduction. Uterine endometrium depends on extrinsic sex steroid input and hence likely has mechanisms that enable adaptation to hormonal variation. Emerging evidence suggests that sex steroid bioavailability in the endometrium is d...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2014-1139
更新日期:2014-11-01 00:00:00
abstract::Vascular smooth muscle cells (SMC) are major constituents of the medial layer of blood vessels and are involved in the development of atherosclerotic plaque. SMC secrete copious IL-6 under basal conditions that can be increased by cytokines such as tumor necrosis factor-alpha and interleukin-1beta (IL-1beta). The goal...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.140.6.6763
更新日期:1999-06-01 00:00:00
abstract::Current drug therapies for obesity are ineffective, and existing treatments for lipid disorders can be further improved. Thyroid hormones affect both conditions, although currently available nonselective thyromimetics are not clinically useful for such treatment due to cardiac side effects. Recent studies suggest that...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2003-0973
更新日期:2004-04-01 00:00:00
abstract::C-type natriuretic peptide (CNP) is produced by the vascular smooth muscle cells (SMCs) of injured and atherosclerotic arteries, in which it may exert autocrine control over SMCs by binding to its principal receptors, NPR-B and NPR-C, but few studies have examined the factors that regulate CNP expression in human SMCs...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2006-0239
更新日期:2006-09-01 00:00:00
abstract::Uterine epithelial cells (UEC) isolated from 6-week-old CF-1 mice were immortalized using retroviral-mediated transfection of SV40 large T-antigen. One line, WEG-1, retained epithelial morphology and reacted with antibodies to cytokeratins 18, 19, laminin, fibronectin, and beta-catenin. In addition, WEG-1 cells displa...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.137.1.8536610
更新日期:1996-01-01 00:00:00
abstract::Pulsatile release of GnRH-1 is critical to stimulate gonadotropes of the anterior pituitary. This secretory pattern seems to be inherent to GnRH-1 neurons, however, the mechanisms underlying such episodical release remain unknown. In monkey nasal explants, the GnRH-1 population exhibits synchronized calcium events wit...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2008-1711
更新日期:2009-07-01 00:00:00
abstract::Livers from fed rats (180-240 g) were perfused noncyclically with a hemoglobin-free medium in vitro to determine whether vasoactive intestinal peptide (VIP) increases hepatic glucose production through a cAMP- or a Ca(2+)-dependent mechanism. Glucose output did not increase, but cAMP increased maximally during 10(-9) ...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.130.4.1372240
更新日期:1992-04-01 00:00:00
abstract::At menopause, the dramatic loss of ovarian estradiol (E2) necessitates the adaptation of estrogen-sensitive neurons in the hypothalamus to an estrogen-depleted environment. We developed a rat model to test the "critical window" hypothesis of the effects of timing and duration of E2 treatment after deprivation on the h...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2015-1032
更新日期:2015-08-01 00:00:00
abstract::Alzheimer's disease (AD) is a progressive neurodegenerative disorder whose etiology is presently unknown. Probably the most consistent and widespread deficit seen in this syndrome is that of the basal forebrain cholinergic system. We have previously demonstrated that estradiol (E2) modulates the function of these neur...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.136.5.7720680
更新日期:1995-05-01 00:00:00
abstract::Pineal denervation by superior cervical ganglionectomy (Gx) decreased high affinity binding of estradiol (E2) to the pineal cytosol of female rats and of testosterone to the cytosol of male rats by 40 and 26% and by 75 and 80%, 5 and 14 days after sugery; hormone binding remained unchanged up to 24 h after surgery. Bi...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-98-4-849
更新日期:1976-04-01 00:00:00
abstract::The mechanisms by which bacterial endotoxin [lipopolysaccharide (LPS)] stimulates the hypothalamo-pituitary-adrenal axis (HPAA) have not been elucidated. The present study was designed to investigate the involvement of macrophages in plasma ACTH and corticosterone responses to LPS administration in rats using selectiv...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-129-1-330
更新日期:1991-07-01 00:00:00
abstract::Prolactin (PRL) is tonically inhibited by dopamine (DA) released from neurons in the arcuate and periventricular nuclei. Kisspeptin plays a pivotal role in LH regulation. In rodents, kisspeptin neurons are found mostly in the anteroventral periventricular and arcuate nuclei, but the physiology of arcuate kisspeptin ne...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2009-1414
更新日期:2010-07-01 00:00:00
abstract::The direct actions of kit-ligand/stem cell factor (KL) in developing ovarian follicles were investigated. Previous studies have shown that granulosa cells express KL that can support oocyte development. The current study demonstrates that KL can also act directly on theca cells to promote cellular growth and different...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.138.9.5368
更新日期:1997-09-01 00:00:00
abstract::3 beta-Hydroxy-5-ene-steroid dehydrogenase/delta 5-delta 4-isomerase (3 beta HSD) is a NAD(+)-dependent membrane-bound enzyme that catalyzes the oxidation of delta 5-3 beta-hydroxysteroids to delta 4-3-keto structures during adrenal, gonadal, and placental steroidogenesis. Enzyme activity is located in both microsomes...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.134.2.8299570
更新日期:1994-02-01 00:00:00
abstract::Thyroid dysfunction during human pregnancy is closely related to serious pregnancy outcome. However, the regulation and function of thyroid hormones during early pregnancy are largely unknown. We found that type II deiodinase, an enzyme converting T4 to activated T3, is highly expressed in the mouse uterus on days 3 a...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2014-1015
更新日期:2014-07-01 00:00:00
abstract::IL-1, secreted by human embryos and trophoblast cells, is important for successful implantation and pregnancy. We previously reported that IL-1beta induced IL-8 production in human endometrial stromal cells (ESCs) and that induction was regulated by substances implicated in implantation. In the present study using hum...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2008-0264
更新日期:2009-01-01 00:00:00
abstract::Neuropeptide Y (NPY) is a powerful orexigenic factor, and alphaMSH is a melanocortin (MC) peptide that induces satiety by activating the MC4 receptor subtype. Genetic models with disruption of MC4 receptor signaling are associated with obesity. In the present study, a 7-day intracerebroventricular infusion to male rat...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.141.12.7842
更新日期:2000-12-01 00:00:00
abstract::T(4) activation into T(3) is catalyzed by type 2 deiodinase (D2) in the brain. The rapid induction of D2 in astrocytes by transient brain ischemia has prompted us to explore the effects of hypoxia on D2 in cultures of astrocytes. Hypoxia (2.5% O(2)) of cultured astrocytes increased D2 activity, alone or in association...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2007-0625
更新日期:2007-10-01 00:00:00
abstract::Excess of glucocorticoids (GCs) is a leading cause of bone fragility, and therapeutic targets are sorely needed. We report that genetic deletion or pharmacological inhibition of proline-rich tyrosine kinase 2 (Pyk2) prevents GC-induced bone loss by overriding GC effects of detachment-induced bone cell apoptosis (anoik...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2019-00237
更新日期:2019-07-01 00:00:00
abstract::Fibroblast growth factor (FGF) 21, a unique, largely liver-derived endocrine member of the FGF superfamily, is often thought of as a fasting factor owing to its induction in rodents during starvation. However, FGF21 is not increased by fasting for periods of <7 days in humans; instead, it rises sharply after acute alc...
journal_title:Endocrinology
pub_type: 杂志文章,评审
doi:10.1210/en.2018-00208
更新日期:2018-05-01 00:00:00
abstract::Male Sprague-Dawley rats were injected ip with 1 microgram pertussis toxin (PTX)/100 g BW. The rats were killed 24, 48, and 72 h after injection, and their pancreases were removed. At each time point, insulin secretion by isolated islets was measured under basal and glucose-stimulated conditions and in the absence and...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.136.5.7720630
更新日期:1995-05-01 00:00:00
abstract::The neuronal growth-associated protein (GAP)-43 has been localized in both long fibers and punctate clusters by immunocytochemistry within the rat anterior pituitary (AP). After adrenalectomy (ADX), GAP-43 immunoreactivity (GAP-43-ir) is greatly increased and is associated with corticotrophs at the light microscopic l...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2005-0715
更新日期:2006-02-01 00:00:00
abstract::Although leptin is a hormone mainly produced by the adipose tissue, it is also produced by the gastric mucosa and the mammary epithelium and is present in maternal milk. The effects of milk leptin on the neonate are not known. The purpose of the investigation was to evaluate the short-term effects of the administratio...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2005-0112
更新日期:2005-06-01 00:00:00
abstract::The maximum amounts of angiotensins II and III that were confined to the kidney during intrarenal arterial administration in conscious dogs were determined to be 2 and 12 pmol/kg X min, respectively. These doses were infused chronically intrarenally to uninephrectomized dogs. A significant reduction in urinary volume ...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-117-5-2160
更新日期:1985-11-01 00:00:00
abstract::Cyclin D1 encodes the regulatory subunit of a holoenzyme that phosphorylates and inactivates the retinoblastoma protein and promotes progression through the G1-S phase of the cell cycle. Amplification or overexpression of cyclin D1 plays pivotal roles in the development of a subset of human cancers including parathyro...
journal_title:Endocrinology
pub_type: 杂志文章,评审
doi:10.1210/en.2004-0959
更新日期:2004-12-01 00:00:00
abstract::Tamoxifen, a partial competitive antagonist to the estrogen receptor, is a potent inhibitor of the proliferation of experimental mammary carcinoma in the rat and is widely used clinically in the treatment of breast cancer. Blockade of estrogen receptors present on neoplastic cells represents the classic mechanism of a...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.130.6.1350760
更新日期:1992-06-01 00:00:00
abstract::Recent evidence has linked mitochondrial dysfunction and DNA damage, increased oxidative stress in skeletal muscle, and insulin resistance (IR). The purpose of this study was to determine the role of the DNA repair enzyme, human 8-oxoguanine DNA glycosylase/apurinic/apyrimidinic lyase (hOGG1), on palmitate-induced mit...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2013-1076
更新日期:2013-08-01 00:00:00
abstract::Sertoli cell intracellular protein 1 (SCc1) and 2 (SCc2) are polypeptides found in rat Sertoli cell cultures incubated with either FSH or (Bu)2cAMP. They were first identified in [35S]methionine-labeled Sertoli cell lysates using two-dimensional gel electrophoresis. Here we extend these observations by showing that SC...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.131.5.1330490
更新日期:1992-11-01 00:00:00
abstract::We have investigated the effects of veratridine, a Na+ channel activator, and ouabain, an inhibitor of Na+-K+-ATPase, on short term (1-h) PRL release from primary cultures of rat anterior pituitary cells and from the rat anterior pituitary cell line GH4C1 in culture. Both compounds should increase intracellular Na+. V...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-113-4-1228
更新日期:1983-10-01 00:00:00
abstract::FSH and IGF-I are both important determinants of testicular development and Sertoli cell function. The present studies were performed to determine the actions of FSH and IGF-I on PI3K/AKT protein kinase signaling in immature rat Sertoli cells. Primary cultures of rat Sertoli cells were prepared from 10-d-old rats. Aft...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.143.6.8838
更新日期:2002-06-01 00:00:00