Abstract:
:Gene related to anergy in lymphocytes (GRAIL) is an E3 ubiquitin ligase that regulates energy in T-lymphocytes. Whereas, the relevance of GRAIL to T lymphocyte function is well established, the role of this protein in other cell types remains unknown. Given that GRAIL is abundant in the liver, we investigated the potential function of GRAIL in nutrient metabolism by generating mice in which the expression of GRAIL is reduced specifically in the liver. Adenovirus-mediated transfer of a short hairpin RNA specific for GRAIL mRNA markedly reduced the amounts of GRAIL mRNA and protein in the liver. Blood glucose levels of the mice with hepatic GRAIL deficiency did not differ from those of control animals in the fasted or fed states. However, these mice manifested glucose intolerance in association with a normal increase in plasma insulin levels during glucose challenge. The mice also manifested an increase in the serum concentration of free fatty acids, whereas the serum levels of cholesterol and triglyceride were unchanged. The hepatic abundance of mRNAs for glucose-6-phosphatase, catalytic (a key enzyme in hepatic glucose production) and for sterol regulatory element-binding transcription factor 1 (an important transcriptional regulator of lipogenesis) was increased in the mice with hepatic GRAIL deficiency, possibly contributing to the metabolic abnormalities of these animals. Our results thus demonstrate that GRAIL in the liver is essential for maintenance of normal glucose and lipid metabolism in living animals.
journal_name
J Mol Endocrinoljournal_title
Journal of molecular endocrinologyauthors
Nakamichi S,Senga Y,Inoue H,Emi A,Matsuki Y,Watanabe E,Hiramatsu R,Ogawa W,Kasuga Mdoi
10.1677/JME-08-0145subject
Has Abstractpub_date
2009-02-01 00:00:00pages
161-9issue
2eissn
0952-5041issn
1479-6813pii
JME-08-0145journal_volume
42pub_type
杂志文章abstract::Previous studies have shown that, in unstimulated mammary epithelial cells from virgin mice, prolactin receptors are retained intracellularly because of their incomplete N-glycosylation. Activation of the nitric oxide/cGMP pathway stimulates Nacetylglucosamine (NAG) transferase I activity, completion of terminal glyco...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/jme.0.0240377
更新日期:2000-06-01 00:00:00
abstract::Unliganded thyroid hormone receptors (apoTRs) repress transcription of hormone-activated genes by recruiting corepressors to the promoters. In contrast, on promoters containing so-called negative thyroid hormone response elements (nTREs), apoTRs activate transcription. A number of different molecular mechanisms have b...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/jme.1.01874
更新日期:2006-06-01 00:00:00
abstract::cAMP-response element-binding protein (CREB) is required for the induction of adipogenic transcription factors such as CCAAT/enhancer-binding proteins (C/EBPs). Interestingly, it is known from studies in other tissues that LKB1 and its substrates AMP-activated protein kinase (AMPK) and salt-inducible kinases (SIKs) ne...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1530/JME-13-0296
更新日期:2014-08-01 00:00:00
abstract::The biologically active metabolite of vitamin D, 1,25-dihydroxyvitamin D3 (VD3), exerts its tissue-specific actions through binding to its intracellular vitamin D receptor (VDR) which functions as a heterodimer with retinoid X receptor (RXR) to recognize vitamin D response elements (VDRE) and activate target genes. Up...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1530/JME-19-0229
更新日期:2020-04-01 00:00:00
abstract::In order to better quantify the molecular mechanisms regulating final oocyte maturation and spawning, complete coding sequences with partially or fully untranslated regions for the steroidogenic enzymes, cytochrome P450 aromatase and 20 beta-hydroxysteroid dehydrogenase, were cloned from ovaries of Atlantic cod (Gadus...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/JME-07-0070
更新日期:2007-10-01 00:00:00
abstract::Parathyroid hormone (PTH) is secreted by the chief cells of the parathyroid gland in response to changes in ionized calcium (Ca(2+)) concentrations. In this study, we measured PTH secretion, and PTH mRNA and calcium-sensing receptor (CaR) mRNA expression by equine parathyroid chief cells in vitro. We also evaluated th...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/jme.0.0310609
更新日期:2003-12-01 00:00:00
abstract::Somatostatins (SSs) play important roles in the growth, development and metabolism of vertebrates. In this study, cDNAs for two unique somatostatin receptor variants were cloned and sequenced from rainbow trout. The two cDNAs, one consisting of 1755 bp and the other of 1743 bp, share 63.6% identity in nucleotide seque...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/jme.0.0320165
更新日期:2004-02-01 00:00:00
abstract::Insulin is important for optimal fetal and neonatal growth and development. Its continued availability is due, in part, to ongoing islet cell growth within the pancreas. IGFs and IGF-binding proteins (IGFBPs) have been implicated as paracrine regulators of islet cell growth within the developing pancreas. The purpose ...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/jme.0.0130049
更新日期:1994-08-01 00:00:00
abstract::Reproductive hormone imbalance in infertile women is correlated to high levels of phthalates and alkylphenols, which are among endocrine-disrupting chemicals (EDCs). Previous studies have shown that they interfere with gene expression by deregulating levels of microRNAs (miRs), small non-coding RNAs targeting mRNAs en...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1530/JME-20-0149
更新日期:2020-11-01 00:00:00
abstract::Eight amino acids are considered essential for human nutrition, and three of them, including leucine, isoleucine and valine, are called as branched-chain amino acids (BCAAs). We recently discovered that dietary deficiency of any BCAA for 7 days rapidly reduces the abdominal fat mass in mice. The goal of this study was...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1530/JME-16-0116
更新日期:2016-11-01 00:00:00
abstract::Hypogonadal (hpg) mutant mice, with a congenital deficiency of hypothalamic gonadotrophin-releasing hormone (GnRH), and testicular feminized (tfm) mice, which lack a functional androgen receptor, were used to study the effects of the potent GnRH agonist 'Zoladex' (ICI 118630; D-Ser (Bu(t))6, Azgly10-GnRH) on pituitary...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/jme.0.0080249
更新日期:1992-06-01 00:00:00
abstract::The mouse knockout of the estrogen receptor alpha (ERalpha) gene, known as alphaERKO, has been extensively used for several years to study the role and function of ERalpha. Residual estradiol binding capacity in uterine tissue of 5-10% raised doubts if this knockout is a genuine null mutation of ERalpha. Although alte...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/jme.0.0290281
更新日期:2002-12-01 00:00:00
abstract::Cellular changes that affect the androgen receptor (AR) can cause prostate cancer to transition from androgen dependent to androgen independent, which is usually lethal. One common change in prostate tumors is overexpression of the AR, which has been shown to lead to androgen-independent growth of prostate cancer cell...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/JME-07-0158
更新日期:2008-07-01 00:00:00
abstract::Whether insulin, at physiological concentrations, has direct effects on vascular smooth muscle cells (VSMCs) remains controversial. Our aim was to characterize the mechanism for insulin resistance in VSMCs. For comparison, the effects of IGF1 and IGF2 were also studied. Cultured human aortic smooth muscle cells (HASMC...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/JME-09-0021
更新日期:2009-12-01 00:00:00
abstract::Neuropathic pain represents one of the most common complications associated with diabetes mellitus (DM) that impacts quality of life. Accumulating studies have highlighted the involvement of miRNAs in DM. Thus, the current study aimed to investigate the roles of miR-155 in diabetic peripheral neuropathy (DPN). In vitr...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1530/JME-19-0067
更新日期:2019-10-01 00:00:00
abstract::Glucagon-like peptide 1 (GLP1) is an intestinal incretin that regulates glucose homeostasis through stimulation of insulin secretion from pancreatic β-cells and inhibits appetite by acting on the brain. Thus, it is a promising therapeutic agent for the treatment of type 2 diabetes mellitus and obesity. Studies using s...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章,评审
doi:10.1530/JME-13-0137
更新日期:2014-06-01 00:00:00
abstract::Prolactin (PRL)-releasing peptide (PrRP) is a strong candidate stimulator of pituitary PRL transcription and secretion in teleosts. However, the role in control of extrapituitary PRL expression is unclear even in mammals. To study the possible presence of PrRP-PRL axes not only in the brain-pituitary but also in perip...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/jme.1.01768
更新日期:2005-06-01 00:00:00
abstract::Using the fluorescent indicators 2',7'-bis(2-carboxyethyl)-5'-(6')-carboxyfluorescein and Oxonol V to monitor intracellular pH (pHi) and cell membrane potential respectively, we have investigated the involvement of H(+)-dependent ATPase and H(+)-dependent K+ channels in the recovery of the rat thyroid cell strain FRTL...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/jme.0.0080079
更新日期:1992-02-01 00:00:00
abstract::Leptin is a cytokine secreted from adipose tissue at a rate commensurate with the size of the body's fat stores. In addition to its anorectic and thermogenic central actions, leptin is known to act on peripheral tissues, including the pancreatic beta-cell where it inhibits insulin secretion and reduces insulin transcr...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/jme.0.0220173
更新日期:1999-04-01 00:00:00
abstract::Pituitary adenylate cyclase-activating polypeptide (PACAP) is synthesized from a precursor, which includes the PACAP-related peptide (PRP; formerly known as GHRH-like peptide). PRP can act as a hypophysiotropic factor in teleosts by stimulating GH secretion. However, no information points to this peptide as a regulato...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1530/JME-10-0065
更新日期:2011-03-03 00:00:00
abstract::Most pro-neuropeptides are processed by the prohormone convertases, PC1 and PC2. We previously reported that changes in thyroid status altered anterior pituitary PC1 mRNA and this regulation was due to triiodothyronine (T(3))-dependent interaction of thyroid hormone receptor (TR) with negative thyroid hormone response...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/jme.0.0330021
更新日期:2004-08-01 00:00:00
abstract::Metformin improves obesity-associated metabolic dysregulation, but has controversial effects on adipose tissue inflammation. The objective of the study is to examine the direct effect of metformin on adipocyte inflammatory responses and elucidate the underlying mechanisms. Adipocytes were differentiated from 3T3-L1 ce...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1530/JME-17-0066
更新日期:2017-07-01 00:00:00
abstract::An isolated in-vitro perifused interrenal gland preparation from the dogfish Scyliorhinus canicula was used to study production of quantitatively the major corticosteroid 1 alpha-hydroxycorticosterone (1 alpha-OH-B), measured by radioimmunoassay. Basal secretory rates were 877.1 +/- 145 (S.E.M.) fmol/mg per 15 min (n ...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/jme.0.0050055
更新日期:1990-08-01 00:00:00
abstract::The effect of steroid hormone treatment on coho salmon (Oncorhynchus kisutch) was examined. The cDNAs for coho salmon FSH beta and LH beta subunits were cloned and sequenced using reverse transcriptase PCR. Northern blot analysis revealed that a single transcript of 1 kb for each of these subunits was present in the p...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/jme.0.0210291
更新日期:1998-12-01 00:00:00
abstract::The aim of our studies was to examine whether IGF-binding protein (IGFBP)-4 is involved in the control of the secretion of various ovarian substances and also the mediation of the effects of several hormones and growth factors on this secretion. For this purpose, we carried out the transfection of porcine granulosa ce...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/jme.0.0260241
更新日期:2001-06-01 00:00:00
abstract::Previous studies have demonstrated that TRH is a potent stimulator of alpha-MSH secretion from frog pituitary melanotrophs. In order to determine the intracellular events responsible for TRH-evoked alpha-MSH release, we have investigated the effect of TRH on polyphosphoinositide breakdown in frog pars intermedia. Neur...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/jme.0.0050129
更新日期:1990-10-01 00:00:00
abstract::Barrett's oesophagus (BO) and oesophageal adenocarcinoma (OAC) are regarded as complications of gastro-oesophageal reflux disease, although all the factors that contribute to the development of these lesions are unknown. Acid suppressive drugs are widely used for symptomatic therapy of reflux disease but may induce hy...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/JME-08-0096
更新日期:2009-04-01 00:00:00
abstract::We have generated hybridomas which secrete monoclonal antibodies to the AT1 subtype of the angiotensin II receptor (AT1 receptor). These were obtained after immunization of Balb C/c mice with synthetic peptides representing sequences from either the extracellular domain (residues 8-17) or the intracellular domain (res...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/jme.0.0110241
更新日期:1993-10-01 00:00:00
abstract::The hyperglycaemia-inducing sulphonamide diazoxide has been previously shown to mediate its effects upon insulin secretion by opening K+ channels and hyperpolarizing the beta-cell membrane. The target site has been characterized as the ATP-regulated K+ (K+ATP) channel protein. In the present study, a detailed investig...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/jme.0.0100059
更新日期:1993-02-01 00:00:00
abstract::In the mouse, GH-binding protein (GHBP) and GH receptor (GHR) are encoded by a single gene via alternative splicing. We previously demonstrated that the steady-state levels of the GHR and GHBP mRNAs are significantly elevated in mouse liver during pregnancy. Hepatic GHR and GHBP mRNAs are associated primarily with one...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/jme.0.0230085
更新日期:1999-08-01 00:00:00