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Article: Quercetin inhibits intestinal non-haem iron absorption by regulating iron metabolism genes in the tissues

Lesjak, Marija / Balesaria, Sara / Skinner, Vernon / Debnam, Edward S / Srai, Surjit Kaila S

European journal of nutrition. 2019 Mar., v. 58, no. 2

2019

Abstract: PURPOSE: There is general agreement that some dietary polyphenols block non-haem iron uptake, but the mechanisms by which they achieve this action are poorly understood. Since the polyphenol quercetin is ingested daily in significant amounts, we have ... ...

Abstract	PURPOSE: There is general agreement that some dietary polyphenols block non-haem iron uptake, but the mechanisms by which they achieve this action are poorly understood. Since the polyphenol quercetin is ingested daily in significant amounts, we have investigated the effect of quercetin on duodenal non-haem iron absorption in vivo, as well as its effect on factors known to be involved in systemic iron metabolism. METHODS: Rats were subject to gastric gavage and systemic quercetin administration. Treatments were followed with uptake studies using radiolabeled iron, serum iron and transferrin saturation measurements, LC-MS/MS analysis of quercetin metabolites in serum, determination of tissue non-haem iron content and analysis of gene expression of iron-related proteins. RESULTS: Both oral and intraperitoneal (IP) quercetin caused serum and tissue iron depletion by two means, first by increasing mucosal iron uptake and inhibiting iron efflux from duodenal mucosa, and second by decreasing levels of duodenal DMT1, Dcytb and FPN. Additionally, IP quercetin induced highly significant increased liver expression of hepcidin, a hormone known to inhibit intestinal iron uptake. CONCLUSIONS: Oral quercetin significantly inhibited iron absorption, while IP quercetin significantly affected iron-related genes. These results could lead to development of new effective ways of preventing and treating iron deficiency anaemia, the most widespread nutritional disorder in the world.
Keywords	blood serum ; genes ; hepcidin ; intestines ; iron ; iron absorption ; iron deficiency anemia ; liquid chromatography ; liver ; metabolites ; mucosa ; nutrient deficiencies ; polyphenols ; quercetin ; radiolabeling ; rats ; tandem mass spectrometry ; transferrin
Language	English
Dates of publication	2019-03
Size	p. 743-753.
Publishing place	Springer Berlin Heidelberg
Document type	Article
ZDB-ID	1466536-0
ISSN	1436-6215 ; 1436-6207
ISSN (online)	1436-6215
ISSN	1436-6207
DOI	10.1007/s00394-018-1680-7
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Quercetin inhibits intestinal non-haem iron absorption by regulating iron metabolism genes in the tissues.

Lesjak, Marija / Balesaria, Sara / Skinner, Vernon / Debnam, Edward S / Srai, Surjit Kaila S

European journal of nutrition

2018 Volume 58, Issue 2, Page(s) 743–753

Abstract: Purpose: There is general agreement that some dietary polyphenols block non-haem iron uptake, but the mechanisms by which they achieve this action are poorly understood. Since the polyphenol quercetin is ingested daily in significant amounts, we have ... ...

Abstract	Purpose: There is general agreement that some dietary polyphenols block non-haem iron uptake, but the mechanisms by which they achieve this action are poorly understood. Since the polyphenol quercetin is ingested daily in significant amounts, we have investigated the effect of quercetin on duodenal non-haem iron absorption in vivo, as well as its effect on factors known to be involved in systemic iron metabolism. Methods: Rats were subject to gastric gavage and systemic quercetin administration. Treatments were followed with uptake studies using radiolabeled iron, serum iron and transferrin saturation measurements, LC-MS/MS analysis of quercetin metabolites in serum, determination of tissue non-haem iron content and analysis of gene expression of iron-related proteins. Results: Both oral and intraperitoneal (IP) quercetin caused serum and tissue iron depletion by two means, first by increasing mucosal iron uptake and inhibiting iron efflux from duodenal mucosa, and second by decreasing levels of duodenal DMT1, Dcytb and FPN. Additionally, IP quercetin induced highly significant increased liver expression of hepcidin, a hormone known to inhibit intestinal iron uptake. Conclusions: Oral quercetin significantly inhibited iron absorption, while IP quercetin significantly affected iron-related genes. These results could lead to development of new effective ways of preventing and treating iron deficiency anaemia, the most widespread nutritional disorder in the world.
MeSH term(s)	Animals ; Antioxidants/pharmacology ; Duodenum/drug effects ; Duodenum/metabolism ; Gene Expression/drug effects ; Intestinal Absorption/drug effects ; Intestinal Mucosa/drug effects ; Intestinal Mucosa/metabolism ; Iron/metabolism ; Male ; Models, Animal ; Quercetin/pharmacology ; Rats ; Rats, Sprague-Dawley
Chemical Substances	Antioxidants ; Quercetin (9IKM0I5T1E) ; Iron (E1UOL152H7)
Language	English
Publishing date	2018-03-28
Publishing country	Germany
Document type	Journal Article
ZDB-ID	1466536-0
ISSN	1436-6215 ; 1436-6207
ISSN (online)	1436-6215
ISSN	1436-6207
DOI	10.1007/s00394-018-1680-7
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Effect of high dose thiamine on the levels of urinary protein biomarkers in diabetes mellitus type 2.

Riaz, Samreen / Skinner, Vernon / Srai, Surjit Kaila

Journal of pharmaceutical and biomedical analysis

2011 Volume 54, Issue 4, Page(s) 817–825

Abstract: The proteomics is known to be a valuable field of study and has become one of the most attractive sub-disciplines in clinical proteomics for human diseases. In the present research work, the levels of urinary protein biomarkers of diabetes mellitus type ... ...

Abstract	The proteomics is known to be a valuable field of study and has become one of the most attractive sub-disciplines in clinical proteomics for human diseases. In the present research work, the levels of urinary protein biomarkers of diabetes mellitus type 2 using proteomic technology have been identified and characterized. Effect of high dose thiamine has also been observed on the levels of these marker proteins. Above 100 type 2 diabetic patients, and 50 same age and sex-matched normal healthy controls were recruited from the Sheikh Zayed Hospital, Lahore, Pakistan and 40 diabetic and 20 control have completed the trial. The urine samples from control and diabetic groups before or after thiamine therapy were further analyzed and identified by 2-D liquid chromatographic system (HPLC) and mass spectrometry MALDI-TOF/TOF and microTOF analysis. All the samples belonging to the control and diabetic groups were then analyzed by ELISA and estimated the levels of some proteins which were found to vary. In the urine samples, the levels of transthyretin, AMBP, haptoglobin precursor were found to decrease while albumin, zinc α 2 glycoprotein, RBP4 and E cadherin were found to increase in the diabetic patients as compared to the controls. The level of albumin in the urine samples of diabetic patients only decreased by 34% after thiamine therapy as compared to the controls and the placebo, while other urinary protein markers did not show a significant change after the therapy. Assessment of the levels of these biomarkers will be helpful in the diagnosis and treatment of diabetes mellitus type 2.
MeSH term(s)	Adult ; Aged ; Albuminuria/drug therapy ; Biomarkers/urine ; Chromatography, High Pressure Liquid ; Diabetes Mellitus, Type 2/complications ; Diabetic Nephropathies/drug therapy ; Diabetic Nephropathies/urine ; Female ; Humans ; Male ; Middle Aged ; Pakistan ; Patient Dropouts ; Proteins/chemistry ; Proteinuria/drug therapy ; Proteomics/methods ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; Tandem Mass Spectrometry ; Thiamine/administration & dosage
Chemical Substances	Biomarkers ; Proteins ; Thiamine (X66NSO3N35)
Language	English
Publishing date	2011-03-25
Publishing country	England
Document type	Controlled Clinical Trial ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	604917-5
ISSN	1873-264X ; 0731-7085
ISSN (online)	1873-264X
ISSN	0731-7085
DOI	10.1016/j.jpba.2010.11.008
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Article: Effect of high dose thiamine on the levels of urinary protein biomarkers in diabetes mellitus type 2

Riaz, Samreen / Skinner, Vernon / Srai, Surjit Kaila

Journal of pharmaceutical and biomedical analysis. 2011 Mar. 25, v. 54, no. 4

2011

Abstract	The proteomics is known to be a valuable field of study and has become one of the most attractive sub-disciplines in clinical proteomics for human diseases. In the present research work, the levels of urinary protein biomarkers of diabetes mellitus type 2 using proteomic technology have been identified and characterized. Effect of high dose thiamine has also been observed on the levels of these marker proteins. Above 100 type 2 diabetic patients, and 50 same age and sex-matched normal healthy controls were recruited from the Sheikh Zayed Hospital, Lahore, Pakistan and 40 diabetic and 20 control have completed the trial. The urine samples from control and diabetic groups before or after thiamine therapy were further analyzed and identified by 2-D liquid chromatographic system (HPLC) and mass spectrometry MALDI-TOF/TOF and microTOF analysis. All the samples belonging to the control and diabetic groups were then analyzed by ELISA and estimated the levels of some proteins which were found to vary. In the urine samples, the levels of transthyretin, AMBP, haptoglobin precursor were found to decrease while albumin, zinc α 2 glycoprotein, RBP4 and E cadherin were found to increase in the diabetic patients as compared to the controls. The level of albumin in the urine samples of diabetic patients only decreased by 34% after thiamine therapy as compared to the controls and the placebo, while other urinary protein markers did not show a significant change after the therapy. Assessment of the levels of these biomarkers will be helpful in the diagnosis and treatment of diabetes mellitus type 2.
Keywords	biomarkers ; cadherins ; enzyme-linked immunosorbent assay ; haptoglobins ; high performance liquid chromatography ; human diseases ; mass spectrometry ; noninsulin-dependent diabetes mellitus ; patients ; prealbumin ; proteomics ; therapeutics ; thiamin ; urine ; zinc ; Pakistan
Language	English
Dates of publication	2011-0325
Size	p. 817-825.
Publishing place	Elsevier B.V.
Document type	Article
ZDB-ID	604917-5
ISSN	0731-7085
ISSN	0731-7085
DOI	10.1016/j.jpba.2010.11.008
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Quercetin inhibits intestinal iron absorption and ferroportin transporter expression in vivo and in vitro.

Lesjak, Marija / Hoque, Rukshana / Balesaria, Sara / Skinner, Vernon / Debnam, Edward S / Srai, Surjit K S / Sharp, Paul A

PloS one

2014 Volume 9, Issue 7, Page(s) e102900

Abstract: Balancing systemic iron levels within narrow limits is critical for maintaining human health. There are no known pathways to eliminate excess iron from the body and therefore iron homeostasis is maintained by modifying dietary absorption so that it ... ...

Abstract	Balancing systemic iron levels within narrow limits is critical for maintaining human health. There are no known pathways to eliminate excess iron from the body and therefore iron homeostasis is maintained by modifying dietary absorption so that it matches daily obligatory losses. Several dietary factors can modify iron absorption. Polyphenols are plentiful in human diet and many compounds, including quercetin--the most abundant dietary polyphenol--are potent iron chelators. The aim of this study was to investigate the acute and longer-term effects of quercetin on intestinal iron metabolism. Acute exposure of rat duodenal mucosa to quercetin increased apical iron uptake but decreased subsequent basolateral iron efflux into the circulation. Quercetin binds iron between its 3-hydroxyl and 4-carbonyl groups and methylation of the 3-hydroxyl group negated both the increase in apical uptake and the inhibition of basolateral iron release, suggesting that the acute effects of quercetin on iron transport were due to iron chelation. In longer-term studies, rats were administered quercetin by a single gavage and iron transporter expression measured 18 h later. Duodenal FPN expression was decreased in quercetin-treated rats. This effect was recapitulated in Caco-2 cells exposed to quercetin for 18 h. Reporter assays in Caco-2 cells indicated that repression of FPN by quercetin was not a transcriptional event but might be mediated by miRNA interaction with the FPN 3'UTR. Our study highlights a novel mechanism for the regulation of iron bioavailability by dietary polyphenols. Potentially, diets rich in polyphenols might be beneficial for patients groups at risk of iron loading by limiting the rate of intestinal iron absorption.
MeSH term(s)	3' Untranslated Regions ; Animals ; Caco-2 Cells ; Cation Transport Proteins/antagonists & inhibitors ; Cation Transport Proteins/genetics ; Cation Transport Proteins/metabolism ; Duodenum/drug effects ; Duodenum/metabolism ; Gene Expression/drug effects ; Homeostasis/physiology ; Humans ; Intestinal Absorption/drug effects ; Intestinal Absorption/physiology ; Intestinal Mucosa/drug effects ; Intestinal Mucosa/metabolism ; Ion Transport/drug effects ; Iron Chelating Agents/pharmacology ; Iron, Dietary/metabolism ; Male ; MicroRNAs/genetics ; MicroRNAs/metabolism ; Quercetin/pharmacology ; Rats ; Rats, Sprague-Dawley
Chemical Substances	3' Untranslated Regions ; Cation Transport Proteins ; Iron Chelating Agents ; Iron, Dietary ; MicroRNAs ; metal transporting protein 1 ; Quercetin (9IKM0I5T1E)
Language	English
Publishing date	2014-07-24
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0102900
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Proteomic identification of human urinary biomarkers in diabetes mellitus type 2.

Riaz, Samreen / Alam, Saadia Shahzad / Srai, Surjit Kaila / Skinner, Vernon / Riaz, Aasma / Akhtar, M Waheed

Diabetes technology & therapeutics

2010 Volume 12, Issue 12, Page(s) 979–988

Abstract: Background: During the proteomic era, one of the most rapidly growing areas in biomedical research is biomarker discovery, particularly using proteomic technologies. The urinary proteome is known to be a valuable field of study and has become one of the ...

Abstract	Background: During the proteomic era, one of the most rapidly growing areas in biomedical research is biomarker discovery, particularly using proteomic technologies. The urinary proteome is known to be a valuable field of study and has become one of the most attractive subdisciplines in clinical proteomics for human diseases. We have described the levels of protein biomarkers specific to diabetes mellitus type 2 in the Pakistani population using proteomic technology. Methods: One hundred type 2 diabetes patients with 50 age- and sex-matched normal healthy controls were recruited from Sheikh Zayed Hospital, Lahore, Pakistan. Urinary proteins were analyzed by two-dimensional liquid chromatography, using chromatofocusing in the first dimension and reverse-phase chromatography in the second, followed by mass spectrometric analysis. Levels of the proteins, which were found to vary in the diabetes type 2 patients compared to the controls, were then determined by enzyme-linked immunosorbent assay in all the samples. Results: Levels of transthyretin, α-1-microglobulin/bikunin precursor, and haptoglobin precursor decreased by 30.8%, 55.2%, and 81.45%, whereas levels of albumin, zinc α2 glycoprotein, retinol binding protein 4, and E-cadherin increased by 486.5%, 29.23%, 100%, and 693%, respectively, in the diabetes patients compared to the controls. Conclusions: Variation in the levels of these identified protein biomarkers have been reported in other pathological states. Assessment of the levels of these biomarkers will be helpful not only in early diagnosis but also in prognosis of diabetes mellitus type 2.
MeSH term(s)	Adult ; Aged ; Albumins/analysis ; Alpha-Globulins/urine ; Biomarkers/urine ; Cadherins/urine ; Carrier Proteins/urine ; Chromatography, Liquid ; Diabetes Mellitus, Type 2/diagnosis ; Diabetes Mellitus, Type 2/urine ; Double-Blind Method ; Female ; Glycoproteins/urine ; Haptoglobins/urine ; Humans ; Male ; Middle Aged ; Pakistan ; Prealbumin/urine ; Proteomics/methods ; Retinol-Binding Proteins, Plasma/urine ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
Chemical Substances	AZGP1 protein, human ; Albumins ; Alpha-Globulins ; Biomarkers ; Cadherins ; Carrier Proteins ; Glycoproteins ; Haptoglobins ; Prealbumin ; RBP4 protein, human ; Retinol-Binding Proteins, Plasma ; alpha-1-microglobulin
Language	English
Publishing date	2010-12
Publishing country	United States
Document type	Journal Article ; Randomized Controlled Trial
ZDB-ID	1452816-2
ISSN	1557-8593 ; 1520-9156
ISSN (online)	1557-8593
ISSN	1520-9156
DOI	10.1089/dia.2010.0078
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: The state of macrophage differentiation determines the TNF alpha response to nitrated lipoprotein uptake.

Smythe, Cheryl D W / Skinner, Vernon O / Bruckdorfer, K Richard / Haskard, Dorian O / Landis, R Clive

Atherosclerosis

2003 Volume 170, Issue 2, Page(s) 213–221

Abstract: Inflammatory cytokine synthesis by monocyte-macrophages in the developing plaque represents an important amplification point in atherosclerotic disease progression. Here we have investigated whether the state of monocyte-macrophage differentiation can ... ...

Abstract	Inflammatory cytokine synthesis by monocyte-macrophages in the developing plaque represents an important amplification point in atherosclerotic disease progression. Here we have investigated whether the state of monocyte-macrophage differentiation can influence TNF alpha synthesis in response to scavenged modified low-density lipoprotein (LDL). We show that LDL modified by nitration induces TNF alpha synthesis when added to undifferentiated human monocytes or a mouse cell line (RAW264.7) bearing an incompletely differentiated phenotype. However, significantly reduced levels of TNF alpha were released from in vitro differentiated human macrophages (P=0.006) or a mouse cell line (IC-21) bearing a well-differentiated macrophage phenotype (P<0.001). A possible scavenging insufficiency in macrophagic cell types was ruled out by lipoprotein-uptake studies and competency to synthesise TNF alpha was confirmed using lipopolysaccharide (LPS) as a stimulus. However, LPS-induced TNF alpha secretion in IC-21 cells was partially suppressed by pre-treatment with nitrated LDL (46%, P=0.0076), with no equivalent effect seen in RAW264.7 cells. Based on these data, we hypothesise that the state of differentiation of intimal monocyte-macrophages may play an important role in their inflammatory response to scavenged modified lipoproteins and that the fully differentiated macrophage end-point may be associated with a non-inflammatory and therefore, atheroprotective, phenotype.
MeSH term(s)	Animals ; Cell Differentiation ; Cell Line ; Enzyme-Linked Immunosorbent Assay ; Humans ; Lipopolysaccharides/pharmacology ; Lipoproteins, LDL/metabolism ; Lipoproteins, LDL/pharmacology ; Macrophages/cytology ; Macrophages/metabolism ; Mice ; Peroxynitrous Acid ; Tumor Necrosis Factor-alpha/biosynthesis
Chemical Substances	Lipopolysaccharides ; Lipoproteins, LDL ; Tumor Necrosis Factor-alpha ; Peroxynitrous Acid (14691-52-2)
Language	English
Publishing date	2003-10
Publishing country	Ireland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80061-2
ISSN	1879-1484 ; 0021-9150
ISSN (online)	1879-1484
ISSN	0021-9150
DOI	10.1016/s0021-9150(03)00285-5
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: The effect of dietary nitrate on salivary, plasma, and urinary nitrate metabolism in humans.

Pannala, Ananth S / Mani, Ali R / Spencer, Jeremy P E / Skinner, Vernon / Bruckdorfer, K Richard / Moore, Kevin P / Rice-Evans, Catherine A

Free radical biology & medicine

2003 Volume 34, Issue 5, Page(s) 576–584

Abstract: Dietary nitrate is metabolized to nitrite by bacterial flora on the posterior surface of the tongue leading to increased salivary nitrite concentrations. In the acidic environment of the stomach, nitrite forms nitrous acid, a potent nitrating/nitrosating ...

Abstract	Dietary nitrate is metabolized to nitrite by bacterial flora on the posterior surface of the tongue leading to increased salivary nitrite concentrations. In the acidic environment of the stomach, nitrite forms nitrous acid, a potent nitrating/nitrosating agent. The aim of this study was to examine the pharmacokinetics of dietary nitrate in relation to the formation of salivary, plasma, and urinary nitrite and nitrate in healthy subjects. A secondary aim was to determine whether dietary nitrate increases the formation of protein-bound 3-nitrotyrosine in plasma, and if dietary nitrate improves platelet function. The pharmacokinetic profile of urinary nitrate excretion indicates total clearance of consumed nitrate in a 24 h period. While urinary, salivary, and plasma nitrate concentrations increased between 4- and 7-fold, a significant increase in nitrite was only detected in saliva (7-fold). High dietary nitrate consumption does not cause a significant acute change in plasma concentrations of 3-nitrotyrosine or in platelet function.
MeSH term(s)	Adult ; Blood Platelets/metabolism ; Blood Proteins/metabolism ; Chromatography, High Pressure Liquid ; Diet ; Female ; Gas Chromatography-Mass Spectrometry ; Humans ; Male ; Metabolic Clearance Rate ; Middle Aged ; Nitrates/pharmacokinetics ; Nitrites/metabolism ; Platelet Aggregation ; Saliva/metabolism ; Tyrosine/analogs & derivatives ; Tyrosine/blood
Chemical Substances	Blood Proteins ; Nitrates ; Nitrites ; 3-nitrotyrosine (3604-79-3) ; Tyrosine (42HK56048U)
Language	English
Publishing date	2003-02-15
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	807032-5
ISSN	1873-4596 ; 0891-5849
ISSN (online)	1873-4596
ISSN	0891-5849
DOI	10.1016/s0891-5849(02)01353-9
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Ghrelin can bind to a species of high density lipoprotein associated with paraoxonase.

Beaumont, Nicholas J / Skinner, Vernon O / Tan, Tricia M-M / Ramesh, Bala S / Byrne, Dominic J / MacColl, Gavin S / Keen, Jeff N / Bouloux, Pierre M / Mikhailidis, Dimitri P / Bruckdorfer, K Richard / Vanderpump, Mark P / Srai, Kaila S

The Journal of biological chemistry

2003 Volume 278, Issue 11, Page(s) 8877–8880

Abstract: Ghrelin is a 28-residue peptide hormone that is principally released from the stomach during fasting and prior to eating. Two forms are present in human plasma: the unmodified peptide and a less abundant acylated version, in which octanoic acid is ... ...

Abstract	Ghrelin is a 28-residue peptide hormone that is principally released from the stomach during fasting and prior to eating. Two forms are present in human plasma: the unmodified peptide and a less abundant acylated version, in which octanoic acid is attached to the third residue, a serine, via an ester linkage. The acylated form of ghrelin acts as a ligand for the growth hormone secretagogue receptor and can stimulate the release of growth hormone from the pituitary gland. It also initiates behavioral and metabolic adaptations to fasting. Here we show that an immobilized form of ghrelin specifically binds a species of high density lipoprotein associated with the plasma esterase, paraoxonase, and clusterin. Both free ghrelin and paraoxon, a substrate for paraoxonase, can inhibit this interaction. An endogenous species of ghrelin is found to co-purify with high density lipoprotein during density gradient centrifugation and subsequent gel filtration. This interaction links the orexigenic peptide hormone ghrelin to lipid transport and metabolism. Furthermore, the interaction of the esterified hormone ghrelin with a species of HDL containing an esterase suggests a possible mechanism for the conversion of ghrelin to des-acyl ghrelin.
MeSH term(s)	Aryldialkylphosphatase ; Centrifugation, Density Gradient ; Chromatography, Affinity ; Chromatography, Gel ; Dose-Response Relationship, Drug ; Electrophoresis, Polyacrylamide Gel ; Esterases/chemistry ; Esterases/metabolism ; Ghrelin ; Growth Hormone/metabolism ; Humans ; Ligands ; Lipid Metabolism ; Lipoproteins, HDL/metabolism ; Paraoxon/chemistry ; Paraoxon/metabolism ; Peptide Hormones/chemistry ; Peptide Hormones/isolation & purification ; Peptide Hormones/metabolism ; Peptides/chemistry ; Peptides/metabolism ; Plasma/metabolism ; Protein Binding ; Protein Structure, Tertiary ; Substrate Specificity ; Ultracentrifugation
Chemical Substances	Ghrelin ; Ligands ; Lipoproteins, HDL ; Peptide Hormones ; Peptides ; ghrelin, des-n-octanoyl ; Growth Hormone (9002-72-6) ; Esterases (EC 3.1.-) ; Aryldialkylphosphatase (EC 3.1.8.1) ; Paraoxon (Q9CX8P80JW)
Language	English
Publishing date	2003-01-16
Publishing country	United States
Document type	Journal Article
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
DOI	10.1074/jbc.C200575200
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Effect of high dose thiamine on the levels of urinary protein biomarkers in diabetes mellitus type 2

Riaz, Samreen / Skinner, Vernon / Srai, Surjit Kaila

Journal of pharmaceutical and biomedical analysis

Volume v. 54,, Issue no. 4

Abstract	The proteomics is known to be a valuable field of study and has become one of the most attractive sub-disciplines in clinical proteomics for human diseases. In the present research work, the levels of urinary protein biomarkers of diabetes mellitus type 2 using proteomic technology have been identified and characterized. Effect of high dose thiamine has also been observed on the levels of these marker proteins. Above 100 type 2 diabetic patients, and 50 same age and sex-matched normal healthy controls were recruited from the Sheikh Zayed Hospital, Lahore, Pakistan and 40 diabetic and 20 control have completed the trial. The urine samples from control and diabetic groups before or after thiamine therapy were further analyzed and identified by 2-D liquid chromatographic system (HPLC) and mass spectrometry MALDI-TOF/TOF and microTOF analysis. All the samples belonging to the control and diabetic groups were then analyzed by ELISA and estimated the levels of some proteins which were found to vary. In the urine samples, the levels of transthyretin, AMBP, haptoglobin precursor were found to decrease while albumin, zinc α 2 glycoprotein, RBP4 and E cadherin were found to increase in the diabetic patients as compared to the controls. The level of albumin in the urine samples of diabetic patients only decreased by 34% after thiamine therapy as compared to the controls and the placebo, while other urinary protein markers did not show a significant change after the therapy. Assessment of the levels of these biomarkers will be helpful in the diagnosis and treatment of diabetes mellitus type 2.
Keywords	zinc ; therapeutics ; thiamin ; urine ; biomarkers ; cadherins ; enzyme-linked immunosorbent assay ; prealbumin ; patients ; mass spectrometry ; noninsulin-dependent diabetes mellitus ; human diseases ; haptoglobins ; proteomics ; high performance liquid chromatography
Language	English
Document type	Article
ISSN	0731-7085
Database	AGRIS - International Information System for the Agricultural Sciences and Technology

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In stock of ZB MED Cologne/Königswinter

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In stock of ZB MED Cologne/Königswinter

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Order via subito

Inter-library loan at ZB MED