Quantitative measurement of full-length and C-terminal proteolyzed RBP4 in serum of normal and insulin-resistant humans using a novel mass spectrometry immunoassay.

Abstract:

:Serum retinol-binding protein 4 (RBP4) levels are increased in insulin-resistant humans and correlate with severity of insulin resistance in metabolic syndrome. Quantitative Western blotting (qWestern) has been the most accurate method for serum RBP4 measurements, but qWestern is technically complex and labor intensive. The lack of a reliable, high-throughput method for RBP4 measurements has resulted in variability in findings in insulin-resistant humans. Many commonly used ELISAs have limited dynamic range. Neither the current ELISAs nor qWestern distinguish among full-length and carboxyl terminus proteolyzed forms of circulating RBP4 that are altered in different medical conditions. Here, we report the development of a novel quantitative mass spectrometry immunoaffinity assay (qMSIA) to measure full-length and proteolyzed forms of RBP4. qMSIA and qWestern of RBP4 were performed in identical serum aliquots from insulin-sensitive/normoglycemic or insulin-resistant humans with impaired glucose tolerance or type 2 diabetes. Total RBP4 qMSIA measurements were highly similar to qWestern and correlated equally well with clinical severity of insulin resistance (assessed by clamp glucose disposal rate, r = -0.74), hemoglobin A1c (r = 0.63), triglyceride/high-density lipoprotein (r = 0.55), waist/hip (r = 0.61), and systolic blood pressure (r = 0.53, all P < 0.001). Proteolyzed forms of RBP4 accounted for up to 50% of total RBP4 in insulin-resistant subjects, and des(Leu)-RBP4 (cleavage of last leucine) correlated highly with insulin resistance (assessed by glucose disposal rate, r = -0.69). In multiple regression analysis, insulin resistance but not glomerular filtration rate was the strongest, independent predictor of serum RBP4 levels. Thus, qMSIA provides a novel tool for accurately measuring serum RBP4 levels as a biomarker for severity of insulin resistance and risk for type 2 diabetes and metabolic syndrome.

journal_name

Endocrinology

journal_title

Endocrinology

authors

Yang Q,Eskurza I,Kiernan UA,Phillips DA,Blüher M,Graham TE,Kahn BB

doi

10.1210/en.2011-1750

subject

Has Abstract

pub_date

2012-03-01 00:00:00

pages

1519-27

issue

3

eissn

0013-7227

issn

1945-7170

pii

en.2011-1750

journal_volume

153

pub_type

杂志文章
  • High glucose stimulates aldosterone-induced hypertrophy via type I mineralocorticoid receptors in neonatal rat cardiomyocytes.

    abstract::Previous studies have shown that aldosterone plus salt loading cause cardiac hypertrophy in rats in vivo, and that in vitro, both aldosterone and glucose stimulate fibroblast growth. The present studies examined the effects of adrenal steroids via mineralocorticoid and glucocorticoid receptors (MR and GR) on [3H]leuci...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo.137.10.8828470

    authors: Sato A,Funder JW

    更新日期:1996-10-01 00:00:00

  • Proadrenomedullin N-terminal 20 peptide increases kinesin's velocity both in vitro and in vivo.

    abstract::Intracellular cargo transport relies on microtubules and motor proteins such as kinesins and dyneins. Currently we have ample knowledge of the mechanisms by which motor proteins propel themselves along the microtubules, but little is known about intracellular factors that regulate motor speed. Here we show that proadr...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/en.2011-1685

    authors: Larráyoz IM,Martínez A

    更新日期:2012-04-01 00:00:00

  • Effects of streptozotocin treatment in growth hormone (GH) and GH antagonist transgenic mice.

    abstract::To investigate GH's role in diabetic end organ damage, experimental diabetes was induced with streptozotocin (STZ) in bovine GH (bGH) or bGH antagonist transgenic mice and in their nontransgenic (NTG) litter mates. Body growth, blood glucose, serum insulin-like growth factor-I levels, liver GH receptor (GHR) binding, ...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo.136.2.7835300

    authors: Chen NY,Chen WY,Bellush L,Yang CW,Striker LJ,Striker GE,Kopchick JJ

    更新日期:1995-02-01 00:00:00

  • Short ghrelin peptides neither displace ghrelin binding in vitro nor stimulate GH release in vivo.

    abstract::Ghrelin is an acylated peptide recently isolated from rat stomach that potently stimulates GH release in vitro and in vivo in rat and man. Ghrelin specifically activates the receptor for the growth hormone secretagogues (GHS-Rla), and it has been proposed as the endogenous ligand mimicked by these synthetic compounds....

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo.143.5.8894

    authors: Torsello A,Ghe' C,Bresciani E,Catapano F,Ghigo E,Deghenghi R,Locatelli V,Muccioli G

    更新日期:2002-05-01 00:00:00

  • GLP-2 Dysregulates Hepatic Lipoprotein Metabolism, Inducing Fatty Liver and VLDL Overproduction in Male Hamsters and Mice.

    abstract::Fundamental complications of insulin resistance and type 2 diabetes include the development of nonalcoholic fatty liver disease and an atherogenic fasting dyslipidemic profile, primarily due to increases in hepatic very-low-density lipoprotein (VLDL) production. Recently, central glucagon-like peptide-2 receptor (GLP2...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/en.2018-00416

    authors: Taher J,Baker C,Alvares D,Ijaz L,Hussain M,Adeli K

    更新日期:2018-09-01 00:00:00

  • Presence of growth hormone-releasing factor-like immunoreactivity in rat duodenum.

    abstract::Growth hormone-releasing factor-like immunoreactivity (GRF-LI) was detected in partially purified extracts of rat hypothalamus and duodenum with a highly specific RIA for rat GRF (rGRF). The concentration of rGRF-LI in the rat hypothalamus was 32.5 fmol/mg dry weight (455 fmol or 3.18 ng/region), while the rat duodenu...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo-117-4-1710

    authors: Bruhn TO,Mason RT,Vale WW

    更新日期:1985-10-01 00:00:00

  • Evidence for a functional association between phosphatidylinositol 3-kinase and c-src in the spreading response of osteoclasts to colony-stimulating factor-1.

    abstract::Osteoclasts are bone-resorbing cells whose normal function depends in part upon their ability to migrate over the bone surface to initiate new sites of bone resorption. The growth factor/cytokine, colony-stimulating factor-1 (CSF-1), potently stimulates osteoclast motility, in a c-src-dependent fashion. The intracellu...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo.141.6.7480

    authors: Grey A,Chen Y,Paliwal I,Carlberg K,Insogna K

    更新日期:2000-06-01 00:00:00

  • Decidual differentiation of stromal cells promotes Proprotein Convertase 5/6 expression and lefty processing.

    abstract::Lefty/Ebaf polypeptides, novel members of the TGF-beta superfamily, are involved in endometrial differentiation and embryo implantation. Recently, we showed that, during undisturbed estrous cycle, lefty is present in mouse uterine horn primarily in a precursor form. Here, we show that decidual differentiation of endom...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/en.2005-0684

    authors: Tang M,Mikhailik A,Pauli I,Giudice LC,Fazelabas AT,Tulac S,Carson DD,Kaufman DG,Barbier C,Creemers JW,Tabibzadeh S

    更新日期:2005-12-01 00:00:00

  • How much of the gonadotropin-releasing hormone (GnRH) surge is required for generation of the luteinizing hormone surge in the ewe? Duration of the endogenous GnRH signal.

    abstract::The preovulatory LH surge in the sheep is accompanied by a massive and sustained surge of GnRH. The objective of this study was to examine the duration of the endogenous GnRH signal required to induce and maintain a LH surge of full amplitude and duration. For this purpose, we assessed the effect of a competitive GnRH...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo.137.11.8895340

    authors: Evans NP,Dahl GE,Caraty A,Padmanabhan V,Thrun LA,Karsch FJ

    更新日期:1996-11-01 00:00:00

  • Involvement of postnatal gonads in the maturation of dopaminergic regulation of prolactin secretion in male rats.

    abstract::Permanent effects of postnatal gonads on dopamine (DA)-mediated regulation of PRL secretion were examined in adult male rats of the Wistar-Imamichi strain. Rats were bilaterally orchidectomized at varying postnatal days, i.e. 8 h after birth [neonatal castration (NC)] or at 1, 2, 3, 4, or 6 weeks of age, and subjected...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo-120-6-2205

    authors: Watanobe H,Takebe K

    更新日期:1987-06-01 00:00:00

  • Almost exclusive androgenic action of dehydroepiandrosterone in the rat mammary gland.

    abstract::To determine the relative role of the androgenic and/or estrogenic components of the action of dehydroepiandrosterone (DHEA) on the histomorphology and structure of the rat mammary gland, ovariectomized (OVX) female animals received DHEA administered alone or in combination with the pure antiandrogen flutamide or the ...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo.139.2.5762

    authors: Sourla A,Martel C,Labrie C,Labrie F

    更新日期:1998-02-01 00:00:00

  • Maintenance and regulation of 17 alpha-hydroxylase expression by bovine thecal cells in primary culture.

    abstract::We have developed and characterized a primary cell culture system to study the regulation of 17 alpha-hydroxylase cytochrome P450 (P45017 alpha) gene expression in bovine thecal cells. Conditions have been established for the dispersal and growth of thecal cells isolated from bovine follicles, which maintain the expre...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo.132.3.7679980

    authors: Demeter-Arlotto M,Rainey WE,Simpson ER

    更新日期:1993-03-01 00:00:00

  • Inhibition of hypothalamic thyrotropin-releasing hormone messenger ribonucleic acid during food deprivation.

    abstract::Food deprivation in laboratory rats induces profound changes in the neuroendocrine system. We have investigated the hypothalamic and pituitary responses of the hypothalamo-pituitary thyroid axis to 48-h food deprivation in Sprague-Dawley rats. Peripheral T3 and hypophysial portal TRH were measured by RIA, and TSH beta...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo-129-5-2714

    authors: Blake NG,Eckland DJ,Foster OJ,Lightman SL

    更新日期:1991-11-01 00:00:00

  • Integrin activates receptor-like protein tyrosine phosphatase alpha, Src, and Rho to increase prolactin gene expression through a final phosphatidylinositol 3-kinase/cytoskeletal pathway that is additive with insulin.

    abstract::We previously showed that receptor-like protein tyrosine phosphatase (RPTP)-alpha inhibited insulin-increased prolactin gene transcription. Others suggested that RPTPalpha was a key intermediary between integrins and activation of Src. We present evidence that inhibition of insulin-increased prolactin gene transcripti...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/en.2004-1386

    authors: Vulin AI,Jacob KK,Stanley FM

    更新日期:2005-08-01 00:00:00

  • Insulin-like growth factor-i regulation of hepatic scavenger receptor class BI.

    abstract::High-density lipoprotein mediates a normal physiological process called reverse cholesterol transport. This process enables the transfer of cholesterol from peripheral tissues to the liver for further metabolism and eventual secretion in the form of bile. The scavenger receptor of the B class (SR-BI), human homolog of...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/en.2004-0330

    authors: Cao WM,Murao K,Imachi H,Yu X,Dobashi H,Yoshida K,Muraoka T,Kotsuna N,Nagao S,Wong NC,Ishida T

    更新日期:2004-12-01 00:00:00

  • Atrial natriuretic peptides: the role of phenylalanine on biological activity.

    abstract::Previous studies have shown that atrial natriuretic peptides (ANPs) inhibit the secretion of aldosterone by isolated rat adrenal glomerulosa cells stimulated by angiotensin II, ACTH, and potassium. Structure-function studies have concentrated on the significance of the C- and N-terminal chains for the biological activ...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo-122-3-826

    authors: Craven TG,Kem DC,Schiebinger RJ

    更新日期:1988-03-01 00:00:00

  • Evidence that the FSH receptor itself is not a calcium channel.

    abstract::FSH has been shown to stimulate the uptake of calcium in cultured rat Sertoli cells, resulting in an increase in cytosolic calcium concentrations. One possibility which has been put forth is that the FSH receptor per se may act as a calcium channel. This is all the more tantalizing given the proposed structure of this...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo.131.2.1379170

    authors: Shibata EF,Matsuda JJ,Volk KA,Collison KA,Segaloff DL

    更新日期:1992-08-01 00:00:00

  • Striated muscle fibers differentiate in primary cultures of adult anterior pituitary cells.

    abstract::Anterior pituitary cells from adult male rats were cultured on a natural extracellular matrix (ECM). From the 5th day, spindle-shaped cells, fusing to form elongated fibers, were observed among the epithelial cells. These fibers later increased in size and number and were identified as striated muscle fibers, based on...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo-122-6-3002

    authors: Spira O,Atzmon R,Rahamim E,Bar-Shavit R,Gross J,Gordon A,Vlodavsky I

    更新日期:1988-06-01 00:00:00

  • Changes in the gene expression of a protein with the cdc10/SWI6 motif, V-1, during rat follicular development and corpus luteum formation.

    abstract::We examined the gene expression of V-1, a novel soluble protein with the cdc10/SWI6 motif, in pseudopregnant rat ovaries. Northern blot analysis on days 1, 5, and 11 of pseudopregnancy revealed an approximately 2-fold increase in the V-1 messenger RNA (mRNA) expression level on day 5 to that on day 1, and no significa...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo.137.4.8625920

    authors: Song SY,Asakai R,Kenmotsu N,Taoka M,Isobe T,Yamakuni T

    更新日期:1996-04-01 00:00:00

  • Comparison of the effects of calcium and magnesium on parathyroid hormone secretion rate in calves.

    abstract::Parathyroid hormone (PTH) secretion rate was measured in seven calves by using a technique which involved RIA of parathyroid venous blood collected during timed intervals and measured volumetrically. Infusion of solutions of NA2EDTA and MgCl2 into the jugular vein was used to alter plasma calcium and magnesium concent...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo-102-6-1803

    authors: Mayer GP,Hurst JG

    更新日期:1978-06-01 00:00:00

  • Prolonged disruption of plasma beta-endorphin dynamics after trauma in the nonhuman primate.

    abstract::Recent evidence has suggested that a circadian rhythm exists for plasma beta-endorphin-like immunoreactivity. The purpose of the present study was to examine the long term effects of surgical trauma on plasma beta-endorphin dynamics. Blood samples for RIA were obtained from female baboons every 4 h for three 48-h peri...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo-120-5-1734

    authors: McIntosh TK

    更新日期:1987-05-01 00:00:00

  • Secretion of pancreatic icosapeptide from porcine pancreas.

    abstract::The pancreatic polypeptide cell, the only mature endocrine cell in the fetal pig pancreas, produces equimolar amounts of two peptides, pancreatic polypeptide and pancreatic icosapeptide, from the same precursor. The amino acid sequence of pancreatic polypeptide is more homogeneous among species, whereas pancreatic ico...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo.142.10.8409

    authors: Amaratunga A,Tuch BE,Han XG,Georges P,Dean SK,Scott H

    更新日期:2001-10-01 00:00:00

  • Transforming growth factor-beta 1 responsiveness of the rat osteocalcin gene is mediated by an activator protein-1 binding site.

    abstract::Osteocalcin (OC), a bone specific protein expressed during differentiation and mineralization of the bone extracellular matrix, is down-regulated upon treatment with transforming growth factor (TGF)-beta 1. To address the potential role of OC gene expression in relation to TGF-beta 1 regulation of bone formation and r...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo.137.5.8612540

    authors: Banerjee C,Stein JL,Van Wijnen AJ,Frenkel B,Lian JB,Stein GS

    更新日期:1996-05-01 00:00:00

  • Activin A regulates porcine follicle-stimulating hormone beta-subunit transcription via cooperative actions of SMADs and FOXL2.

    abstract::Activins stimulate FSH synthesis and secretion by pituitary gonadotrope cells. Activin A induction of porcine and murine FSHβ (Fshb) gene transcription in immortalized gonadotropes is dependent on homolog of Drosophila mothers against decapentaplegic (SMAD) proteins as well as the forkhead transcription factor L2 (FOX...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/en.2010-0605

    authors: Lamba P,Wang Y,Tran S,Ouspenskaia T,Libasci V,Hébert TE,Miller GJ,Bernard DJ

    更新日期:2010-11-01 00:00:00

  • Unexpected inhibitory action of N-methyl-D,L-aspartate or luteinizing hormone release in adult ovariectomized rhesus monkeys: a role of the hypothalamic-adrenal axis.

    abstract::N-methyl-D,L,-aspartate (NMA), an analog of the excitatory neurotransmitter aspartate, has been previously shown to acutely stimulate LH release in the rodent and primate. In this study, we examine the effect of NMA on LH secretion in the long term ovariectomized adult rhesus monkey. After a 3-h control period, three ...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo-127-2-724

    authors: Reyes A,Luckhaus J,Ferin M

    更新日期:1990-08-01 00:00:00

  • Escape from the sodium-retaining action of intrarenal angiotensins II and III in the conscious dog.

    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

    authors: Dickstein GM,Woodson JF,Lamb NE,Rose CE Jr,Peach MJ,Carey RM

    更新日期:1985-11-01 00:00:00

  • Activin-binding protein is present in pituitary.

    abstract::A binding protein for activin was purified from bovine pituitary by affinity chromatography on dextran sulfate-Sepharose CL-4B and activin-Affi-Gel 10. A 52,700-fold purification over the starting crude homogenate was achieved. The purified preparation showed two bands of 36 and 33 kilodalton in sodium dodecyl sulfate...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo-128-3-1434

    authors: Kogawa K,Nakamura T,Sugino K,Takio K,Titani K,Sugino H

    更新日期:1991-03-01 00:00:00

  • Antagonists of GHRH decrease production of GH and IGF-I in MXT mouse mammary cancers and inhibit tumor growth.

    abstract::The involvement of IGF-I in mammary carcinogenesis is well established, but the role of GH, as an autocrine growth factor for breast cancers is poorly understood. The goal of our study was to investigate whether antagonists of GHRH can interfere with the effects of GH and IGF-I in MXT mouse mammary cancers. GHRH antag...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo.142.10.8426

    authors: Szepeshazi K,Schally AV,Armatis P,Groot K,Hebert F,Feil A,Varga JL,Halmos G

    更新日期:2001-10-01 00:00:00

  • Inhibition of transcription affects synthesis of steroidogenic acute regulatory protein and steroidogenesis in MA-10 mouse Leydig tumor cells.

    abstract::Hormonal induction of steroidogenesis in the adrenal and gonads is dependent on the synthesis and function of the steroidogenic acute regulatory protein (StAR). As a first approach to investigate the role of translation in the control of StAR expression, we examined StAR protein synthesis and steroid production in MA-...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo.138.11.5535

    authors: Clark BJ,Combs R,Hales KH,Hales DB,Stocco DM

    更新日期:1997-11-01 00:00:00

  • Reevaluation of the role of cyclic adenosine 3',5'-monophosphate and protein kinase in the stimulation of steroidogenesis by luteinizing hormone in bovine corpus luteum slices.

    abstract::Incubation of bovine corpus luteum slices at 37 C with luteinizing hormone showed that 10.0 microng LH/ml caused a maximum rise in tissue cyclic AMP content within 15 min. Slices incubated with 1.0 or 0.1 microng LH/ml showed a much more gradual accumulation of this nucleotide. In the absence of added LH, a marked dec...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo-100-6-1571

    authors: Ling WY,Marsh JM

    更新日期:1977-06-01 00:00:00