Abstract:
:Specific retinoid X receptor (RXR) agonists, such as LG100268 (LG268), and the thiazolidinedione (TZD) PPARgamma agonists, such as rosiglitazone, produce insulin sensitization in rodent models of insulin resistance and type 2 diabetes. In sharp contrast to the TZDs that produce significant increases in body weight gain, RXR agonists reduce body weight gain and food consumption. Unfortunately, RXR agonists also suppress the thyroid hormone axis and generally produce hypertriglyceridemia. Heterodimer-selective RXR modulators have been identified that, in rodents, retain the metabolic benefits of RXR agonists with reduced side effects. These modulators bind specifically to RXR with high affinity and are RXR homodimer partial agonists. Although RXR agonists activate many heterodimer partners, these modulators selectively activate RXR:PPARalpha and RXR:PPARgamma, but not RXR:RARalpha, RXR:LXRalpha, RXR:LXRbeta, or RXR:FXRalpha. We report the in vivo characterization of one RXR modulator, LG101506 (LG1506). In Zucker fatty (fa/fa) rats, LG1506 is a potent insulin sensitizer that also enhances the insulin-sensitizing activities of rosiglitazone. Administration of LG1506 reduces both body weight gain and food consumption and blocks the TZD-induced weight gain when coadministered with rosiglitazone. LG1506 does not significantly suppress the thyroid hormone axis in rats, nor does it elevate triglycerides in Sprague Dawley rats. However, LG1506 produces a unique pattern of triglycerides elevation in Zucker rats. LG1506 elevates high-density lipoprotein cholesterol in humanized apolipoprotein A-1-transgenic mice. Therefore, selective RXR modulators are a promising approach for developing improved therapies for type 2 diabetes, although additional studies are needed to understand the strain-specific effects on triglycerides.
journal_name
Endocrinologyjournal_title
Endocrinologyauthors
Leibowitz MD,Ardecky RJ,Boehm MF,Broderick CL,Carfagna MA,Crombie DL,D'Arrigo J,Etgen GJ,Faul MM,Grese TA,Havel H,Hein NI,Heyman RA,Jolley D,Klausing K,Liu S,Mais DE,Mapes CM,Marschke KB,Michellys PY,Montrose-Rafidoi
10.1210/en.2005-0690subject
Has Abstractpub_date
2006-02-01 00:00:00pages
1044-53issue
2eissn
0013-7227issn
1945-7170pii
en.2005-0690journal_volume
147pub_type
杂志文章相关文献
ENDOCRINOLOGY文献大全abstract::Hypoglycemia associated with diabetes management is a potential risk for cardiovascular diseases. However, the effect of hypoglycemic episodes including a surge of sympathetic activity on the progression of neointima formation after vascular injury remains largely unknown. In this study, insulin was injected intraperi...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2013-1628
更新日期:2014-06-01 00:00:00
abstract::We have investigated the physiological regulation and functional significance of brain-derived neurotrophic factor (BDNF) in the endocrine melanotrope cells of the pituitary pars intermedia of the amphibian Xenopus laevis, which can adapt its skin color to the light intensity of its environment. In black-adapted anima...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.143.4.8721
更新日期:2002-04-01 00:00:00
abstract::The Ca2+ response of individual cells to TRH was investigated in excitable pituitary GH3 and in nonexcitable Hela cells transfected with the TRH receptor complementary DNA (HelaR cells). GH3 cells typically responded to 1 microM TRH with an immediate transient [Ca2+]i spike (mean peak [Ca2+]i = 1.5 microM) followed by...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.135.3.8070350
更新日期:1994-09-01 00:00:00
abstract::Ca2+ influx through voltage-gated Ca2+ channels (VGCCs) plays a key role in GH secretion. In this review, we summarize the current state of knowledge regarding the physiology and molecular machinery of VGCCs in pituitary somatotrophs. We next discuss the possible involvement of Ca2+ channelopathies in pituitary diseas...
journal_title:Endocrinology
pub_type: 杂志文章,评审
doi:10.1210/en.2018-00743
更新日期:2018-12-01 00:00:00
abstract::The very low density lipoprotein/apolipoprotein-E receptor (VLDLR) is the newest member of the low density lipoprotein receptor (LDLR) family. Very little is known about VLDLR localization and regulation. Immunohistochemical analysis of human placenta with a specific polyclonal antibody detected VLDLR in syncytiotroph...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.136.1.7828550
更新日期:1995-01-01 00:00:00
abstract::Stimulators of bone resorption, such as PTH, 1,25-dihydroxycholecalciferol [1,25-(OH)2D3], or prostaglandin E2 (PGE2), do not cause calcium release from cultured calvaria of the genetically determined osteopetrotic microphthalmic (mi/ mi) mouse, due to a defect in the function of osteoclasts. To investigate the capaci...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-112-3-945
更新日期:1983-03-01 00:00:00
abstract::We have examined the effects of acute administration of the cannabinoid receptor type 1 (CB(1)) antagonist AM251 on the rat hypothalamic-pituitary-adrenal (HPA) axis with respect to both gender and time of day. Blood samples were collected from conscious male and female rats every 5 min using an automated blood sampli...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2010-0101
更新日期:2010-08-01 00:00:00
abstract::Differences in the catalytic activity of the placental and gonadal isozymes of porcine aromatase cytochrome P450 (P450arom) were examined in cell lines exhibiting stable expression of recombinant enzyme. Cell lines were selected that expressed high, but similar, immunodetectable levels of each isozyme based on Western...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.140.11.7140
更新日期:1999-11-01 00:00:00
abstract::Prader-Willi syndrome (PWS) has a biphasic clinical phenotype with failure to thrive in the neonatal period followed by hyperphagia and severe obesity commencing in childhood among other endocrinological and neurobehavioral abnormalities. The syndrome results from loss of function of several clustered, paternally expr...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2005-0371
更新日期:2005-10-01 00:00:00
abstract::ACTH produced a 75% increase in pregnenolone biosynthesis from endogenous precursors in isolated cells prepared from the rat Snell adrenocortical carcinoma 494. On the addition of 24- and 25-hydroxycholesterol to the tumor cells, the rate of pregnenolone synthesis increased 10-fold but was insensitive to the presence ...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-105-5-1230
更新日期:1979-11-01 00:00:00
abstract::PTHrP is produced in vessels and acts as a local modulator of tone. We recently reported that PTHrP(1-34) is able to induce vasorelaxation in rat uterine arteries, but in pregnancy, this response is blunted and becomes strictly endothelium dependent. The present study aimed to get insights into the mechanisms involved...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2007-0568
更新日期:2008-02-01 00:00:00
abstract::The effects of insulin treatment and dietary glucose on the responsiveness of adipose tissue to insulin and GH after hypophysectomy were studied. Male rats, 130-150 g, were hypophysectomized. Glucose metabolism was measured by determining the production of CO2 from [14C]glucose and the incorporation of glucose into li...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-116-3-945
更新日期:1985-03-01 00:00:00
abstract::The presence of estrogen receptors (ERs) in nonneural cells in brain, including glia, ependyma, and endothelia, has not previously been documented with electron microscopy. This study employed immunocytochemistry to investigate whether ER immunoreactivity (ER-ir) is present in glial, ependymal, or endothelial cells in...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.130.1.1727710
更新日期:1992-01-01 00:00:00
abstract::GH and insulin-like growth factor (IGF)-I are important components of the growth axis. We undertook to determine how plasma levels of these hormones altered with different seasonal and nutritional states in young male red deer to provide an insight into how the growth axis changes under these conditions. Growth rate a...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.137.2.8593820
更新日期:1996-02-01 00:00:00
abstract::To assess a possible regulatory influence of opioids upon anterior pituitary function in the chimpanzee, we evaluated the effects of the specific opiate receptor antagonist naloxone and the agonistic enkephalin analog [D-Ala2, MePhe4,Met(o)-ol]enkephalin (FK 33-824; Sandoz) on serum levels of PRL, cortisol, FSH, and L...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-112-6-2168
更新日期:1983-06-01 00:00:00
abstract::A central step in the development and sexual differentiation of the brain is the intraneuronal conversion of testosterone to estrogen. This conversion is catalyzed by an enzyme complex comprised of cytochrome P450 aromatase and the ubiquitous NADPH-dependent cytochrome P450 reductase. Brain aromatase activity is devel...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.135.4.7925130
更新日期:1994-10-01 00:00:00
abstract::Isolated renal cortical slices were used to study the conversion of 25-hydroxyvitamin D3 to 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] and 24,25-dihydroxyvitamin D3 [24,25](OH2)D3] by the rat kidney. Production of 1,25-(OH)2D3 and 24,25-(OH)2D3 was linear with time (30-90 min) and tissue weight (40-250 mg). Production of...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-109-1-218
更新日期:1981-07-01 00:00:00
abstract::To test the hypothesis that insulin mediators serve as the signal transduction system for insulin's steroidogenic actions in human placental cytotrophoblasts, we examined the effects of two inositolglycan insulin mediators, the insulin pH 2.0 chiro-inositol mediator (IM-pH 2.0) and the insulin pH 1.3 myo-inositol medi...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-129-6-2951
更新日期:1991-12-01 00:00:00
abstract::Loss of circulating 17β-estradiol (E2) that occurs during menopause can have detrimental effects on cognitive function. The efficacy of hormone replacement therapy declines as women become farther removed from the menopausal transition, yet the molecular mechanisms underlying this age-related switch in E2 efficacy are...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2015-1514
更新日期:2015-11-01 00:00:00
abstract::Thyroid hormone (TH) is required for frog metamorphosis, and corticosterone (CORT) increases TH signaling to accelerate metamorphic progression. However, a requirement for CORT in metamorphosis has been difficult to assess prior to the recent development of gene-editing technologies. We addressed this long-standing qu...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endocr/bqaa193
更新日期:2020-12-01 00:00:00
abstract::In different types of mammalian cells, insulin has been shown to promote the release of an inositol phosphate glycan (InsP-glycan) through the hydrolysis of a glycosyl-phosphatidylinositol (glycosyl-PtdIns). This InsP-glycan, which has been demonstrated to be taken up by intact cells, may mediate some of the biologica...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.134.3.8119190
更新日期:1994-03-01 00:00:00
abstract::L-700,653 is a potent nonpeptidyl GH secretagogue consisting of a benzolactam structure: (4'-[[3(R)-[[3-[(2(S),3-dihydroxypropyl) amino]3-methyl-1-oxobutyl]amino]2,3,4,5-tetrahydro-2-oxo-1H-1-benzaze pin- 1-yl]methyl][1,1'-biphenyl]2-carboxamide hydrochloride). When administered sc by a Medi-Jector device at 0, 0.003,...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.136.3.7867560
更新日期:1995-03-01 00:00:00
abstract::Leukemia Inhibitory Factor (LIF) and its receptors in human and mouse pituicytes are expressed abundantly in corticotrophs and somatotrophs. As LIF induces POMC transcription and LPS-mediated stress also induces hypothalamic and pituitary LIF expression, we studied ACTH secretion in LIF knockout (LIF KO) mice. Basal A...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.137.7.8770940
更新日期:1996-07-01 00:00:00
abstract::Twelve weeks of high-fat diet feeding causes ghrelin resistance in arcuate neuropeptide Y (NPY)/agouti-related protein (AgRP) neurons. In the current study, we investigated whether diet-induced weight loss could restore NPY/AgRP neuronal responsiveness to ghrelin and whether ghrelin mediates rebound weight gain after ...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2012-1421
更新日期:2013-02-01 00:00:00
abstract::Angiotensin II is a potent octapeptide vasoconstrictor and regulator of cardiovascular and electrolyte homeostasis. Angiotensinogen, the protein precursor of angiotensin II, is synthesized by the liver and many other organs of the adult rat. To determine whether angiotensin may be present in early fetal development we...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-121-4-1335
更新日期:1987-10-01 00:00:00
abstract::Exogenous glucocorticoids are potent inhibitors of skeletal growth in experimental animals and children. The mechanism whereby glucocorticoids exert this effect is unclear, and circulating somatomedin levels have been reported to be low, normal, or high in this situation. Since recent studies have emphasized the impor...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-125-1-165
更新日期:1989-07-01 00:00:00
abstract::3-Iodothyronamine (3-T1AM) is an endogenous thyroid hormone (TH)-derived metabolite that induces severe hypothermia in mice after systemic administration; however, the underlying mechanisms have remained enigmatic. We show here that the rapid 3-T1AM-induced loss in body temperature is a consequence of peripheral vasod...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2016-1951
更新日期:2017-06-01 00:00:00
abstract::We previously reported that dexamethasone (DEX) induces dose-dependent biphasic effects on steady state somatostatin (SS) messenger RNA (mRNA) levels in normal rat islet and islet SS-producing tumor cells (1027B2), characterized by stimulation at low doses and marked inhibition at high doses. The stimulatory effect is...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.136.6.7750460
更新日期:1995-06-01 00:00:00
abstract::Cushing's disease (CD) is a rare condition in which hypercortisolemia is secondary to excessive ACTH release from a pituitary corticotroph adenoma. CD is associated with significant morbidity and mortality, and a safe therapy that effectively targets the pituitary tumor is still lacking. Retinoic acid (RA) and dopamin...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2013-1820
更新日期:2014-09-01 00:00:00
abstract::We recently reported that bone morphogenetic proteins (BMPs) 2 and 4 can stimulate FSHbeta-subunit (Fshb) transcription alone and in synergy with activins. We further showed that BMP2 signals via the BMP type IA receptor (or activin receptor-like kinase 3) to mediate its effects. However, the intracellular mechanisms ...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2010-0071
更新日期:2010-07-01 00:00:00