Excessive Iron Induces Oxidative Stress Promoting Cellular Perturbations and Insulin Secretory Dysfunction in MIN6 Beta Cells.

Blesia, V., Patel, V.B., Al-Obaidi, H., Renshaw, D. and Zariwala, M. 2021. Excessive Iron Induces Oxidative Stress Promoting Cellular Perturbations and Insulin Secretory Dysfunction in MIN6 Beta Cells. Cells. 10 (5) 1141. https://doi.org/10.3390/cells10051141

TitleExcessive Iron Induces Oxidative Stress Promoting Cellular Perturbations and Insulin Secretory Dysfunction in MIN6 Beta Cells.
TypeJournal article
AuthorsBlesia, V., Patel, V.B., Al-Obaidi, H., Renshaw, D. and Zariwala, M.
Abstract

Exposure to high levels of glucose and iron are co-related to reactive oxygen species (ROS) generation and dysregulation of insulin synthesis and secretion, although the precise mechanisms are not well clarified. The focus of this study was to examine the consequences of exposure to high iron levels on MIN6 β-cells. MIN6 pseudoislets were exposed to 20 µM (control) or 100 µM (high) iron at predefined glucose levels (5.5 mM and 11 mM) at various time points (3, 24, 48, and 72 h). Total iron content was estimated by a colourimetric FerroZine™ assay in presence or absence of transferrin-bound iron. Cell viability was assessed by a resazurin dye-based assay, and ROS-mediated cellular oxidative stress was assessed by estimating malondialdehyde levels. β-cell iron absorption was determined by a ferritin immunoassay. Cellular insulin release and content was measured by an insulin immunoassay. Expression of SNAP-25, a key protein in the core SNARE complex that modulates vesicle exocytosis, was measured by immunoblotting. Our results demonstrate that exposure to high iron levels resulted in a 15-fold (48 h) and 4-fold (72 h) increase in cellular iron accumulation. These observations were consistent with data from oxidative stress analysis which demonstrated 2.7-fold higher levels of lipid peroxidation. Furthermore, exposure to supraphysiological (11 mM) levels of glucose and high iron (100 µM) at 72 h exerted the most detrimental effect on the MIN6 β-cell viability. The effect of high iron exposure on total cellular iron content was identical in the presence or absence of transferrin. High iron exposure (100 µM) resulted in a decrease of MIN6 insulin secretion (64% reduction) as well as cellular insulin content (10% reduction). Finally, a significant reduction in MIN6 β-cell SNAP-25 protein expression was evident at 48 h upon exposure to 100 µM iron. Our data suggest that exposure to high iron and glucose concentrations results in cellular oxidative damage and may initiate insulin secretory dysfunction in pancreatic β-cells by modulation of the exocytotic machinery.

Keywordsexcess iron
oxidative stress
impaired insulin secretion
type 2 diabetes mellitus
β-cell
Article number1141
JournalCells
Journal citation10 (5)
ISSN2073-4409
Year2021
PublisherMDPI
Publisher's version
License
CC BY 4.0
File Access Level
Open (open metadata and files)
Digital Object Identifier (DOI)https://doi.org/10.3390/cells10051141
Publication dates
Published09 May 2021

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Mehta, K., Greenwell, P., Renshaw, D., Busbridge, Mark, Garcia, M, Farnaud, S. and Patel, V. B. 2015. Characterisation of hepcidin response to holotransferrin treatment in CHO TRVb-1 cells. Blood Cells, Molecules, and Diseases. 55 (2), pp. 110-118. https://doi.org/10.1016/j.bcmd.2015.05.002

Acute hypoxia reduces plasma myostatin independent of hypoxic dose
Elliott, B., Simonson, T.S., Getting, S.J., Renshaw, D., Wagner Peter, D. and MacKenzie, R. 2015. Acute hypoxia reduces plasma myostatin independent of hypoxic dose. 8th International Conference on Cachexia, Sarcopenia and Muscle Wasting. Paris 04 - 06 Dec 2015 The Society on Sarcopenia, Cachexia and Wasting Disorders.

Betaine, in context
Mehta, K. and Patel, V. 2015. Betaine, in context. in: Preedy, V.R. (ed.) Betaine: chemistry, analysis, function and effects Royal Society of Chemistry.

Formulation and characterization of curcumin loaded DQAsomes for pulmonary delivery
Zupancic, S., Kocbek, P., Kristl, J., Zariwala, M., Renshaw, D., Gul, M.O., Elsaid, Z., Taylor, K.M.G. and Somavarapu, S. 2014. Formulation and characterization of curcumin loaded DQAsomes for pulmonary delivery. 10th International Conference and Workshop on Biological Barriers. Saarbrücken 16 - 21 Feb 2014

Serum ferritin levels are correlated with total adiposity, but not BMI in obese males
Zariwala, M., Kosicka, A., MacKenzie, R. and Renshaw, D. 2014. Serum ferritin levels are correlated with total adiposity, but not BMI in obese males. Society for Endocrinology BES 2014. Liverpool, UK 24 - 27 Mar 2014 BioScientifica Ltd.. https://doi.org/10.1530/endoabs.34.P255

A human cell model of Parkinson’s disease confirms iron accumulation in dopaminergic neurons following 6-OHDOPA treatment
Zariwala, M. and Farnaud, S. 2014. A human cell model of Parkinson’s disease confirms iron accumulation in dopaminergic neurons following 6-OHDOPA treatment. European Iron Club Annual Meeting 2014. Verona, Italy 11 - 14 Sep 2014

Fabrication and characterization of novel hydrophobically modified chitosan nanoliposomes for oral iron delivery
Zariwala, M., Bendre, H., Markiv, A., Farnaud, S., Somavarapu, S. and Renshaw, D. 2014. Fabrication and characterization of novel hydrophobically modified chitosan nanoliposomes for oral iron delivery. European Iron Club Annual Meeting 2014. Verona, Italy 11 - 14 Sep 2014

Design and Development of Novel Mitochondrial Targeted Nanocarriers, DQAsomes for Curcumin Inhalation
Zupančič, Š., Kocbek, P., Zariwala, M., Renshaw, D., Gul, M.O., Elsaid, Z., Taylor, K.M.G. and Somavarapu, S. 2014. Design and Development of Novel Mitochondrial Targeted Nanocarriers, DQAsomes for Curcumin Inhalation. Molecular Pharmaceutics. 11 (7), pp. 2334-2345. https://doi.org/10.1021/mp500003q

Ascorbyl palmitate/DSPE-PEG nanocarriers for oral iron delivery:Preparation, characterisation and in vitro evaluation
Zariwala, M., Farnaud, S., Merchant, Z., Somavarapu, S. and Renshaw, D. 2014. Ascorbyl palmitate/DSPE-PEG nanocarriers for oral iron delivery:Preparation, characterisation and in vitro evaluation. Colloids and Surfaces B: Biointerfaces. 115 (1), p. 86– 92. https://doi.org/10.1016/j.colsurfb.2013.11.028

Design and Development of Novel Mitochondrial Targeted
Zupančič, Š., Kocbek, P., Zariwala, M., Renshaw, D., Gul, M.O., Elsaid, Z., Taylor, K.M.G. and Somavarapu, S. 2014. Design and Development of Novel Mitochondrial Targeted. Molecular Pharmaceutics. 11 (7), pp. 2334-2345. https://doi.org/10.1021/mp500003q

Acute hypoxia alters myotube size in vitro and myostatin signalling in vivo
Elliott, B., Renshaw, D., Getting, S.J., Watt, P.W. and MacKenzie, R. 2014. Acute hypoxia alters myotube size in vitro and myostatin signalling in vivo. FASEB. San Diego Jul 2015 Federation of American Societies for Experimental Biology.

The role of acute hypoxia in skeletal muscle atrophy
Elliott, B., Renshaw, D., Getting, S.J., Watt, P., Howard, D. and MacKenzie, R. 2014. The role of acute hypoxia in skeletal muscle atrophy. Physiology. London 30 Jun 2014 The Physiological Society.

Cardiovascular disease in aging and the role of oxidative stress
Alzaid, F., Patel, V. and Preedy, V.R. 2014. Cardiovascular disease in aging and the role of oxidative stress. in: Preedy, V.R. (ed.) Aging: oxidative stress and dietary antioxidants Academic Press. pp. 23-36

Ascorbyl palmitate/DSPE-PEG nanocarriers for oral iron delivery: Preparation, characterisation and in vitro evaluation
Zariwala, M.G., Farnaud, S., Merchant, Z., Somavarapu, S. and Renshaw, D. 2014. Ascorbyl palmitate/DSPE-PEG nanocarriers for oral iron delivery: Preparation, characterisation and in vitro evaluation. Colloids and Surfaces B: Biointerfaces. 115 (3), pp. 86-92. https://doi.org/10.1016/j.colsurfb.2013.11.028

The branched-chain aminotransferase proteins: novel redox chaperones for protein disulfide isomerase: implications in Alzheimer’s disease
Conway, M.E., El Hindy, M., Hezwani, M., Hull, J., Corry, D., Mansbridge, A., Hassler, M., Patel, V., Kehoe, P.G., Love, S., Harris, M., Forshaw, T., Lee, C.S., El Amraoui, F. and Wilson, A. 2014. The branched-chain aminotransferase proteins: novel redox chaperones for protein disulfide isomerase: implications in Alzheimer’s disease. Antioxidants and Redox Signaling. 20 (16), pp. 2497-2513. https://doi.org/10.1089/ars.2012.4869

Design and development of novel mitochondrial targeted nanocarriers, DQAsomes for curcumin inhalation
Zupančič, Š., Kocbek, P., Zariwala, M.G., Renshaw, D., Gul, M.O., Elsaid, Z., Taylor, K. and Somavarapu, S. 2014. Design and development of novel mitochondrial targeted nanocarriers, DQAsomes for curcumin inhalation. Molecular Pharmaceutics. 11 (7), pp. 2334-2345. https://doi.org/10.1021/mp500003q

A novel approach to oral iron delivery using ferrous sulphate loaded solid lipid nanoparticles
Gulrez Zariwala, M., Elsaid, N., Jackson, T.L., Corral López, F., Farnaud, S., Somavarapu, S. and Renshaw, D. 2013. A novel approach to oral iron delivery using ferrous sulphate loaded solid lipid nanoparticles. International Journal of Pharmaceutics. 456 (2), pp. 400-407. https://doi.org/10.1016/j.ijpharm.2013.08.070

Annexin-A1 protein and its relationship to cortisol in human saliva
Fowkes, R.C., Moradi-Bidhendi, N., Branceleone, V., Gulrez Zariwala, M., Brady, D., Jessop, D.S., Perretti, M., Renshaw, D. and Brancaleone, V. 2013. Annexin-A1 protein and its relationship to cortisol in human saliva. Psychoneuroendocrinology. 38 (5), pp. 722-727. https://doi.org/10.1016/j.psyneuen.2012.08.003

Macronutrient regulation of PYY and DPPIV in human intestinal epithelial cells
Zariwala, M., Kosicka, A. and Renshaw, D. 2013. Macronutrient regulation of PYY and DPPIV in human intestinal epithelial cells. ENDO 2013: The Endocrine Society’s 95th Annual Meeting. San Francisco, USA 15 - 18 Jun 2013

Preparation and Characterisation of Solid Lipid Particles for Oral Iron Delivery
Zariwala, M., Farnaud, S., Somavarapu, S. and Renshaw, D. 2013. Preparation and Characterisation of Solid Lipid Particles for Oral Iron Delivery. Fifth Congress of the International BioIron Society (IBIS), Biennial World Meeting. University College London 14 - 18 Apr 2013 Wiley. https://doi.org/10.1002/ajh.23453

Hepcidin transcription and peptide secretion are governed by different regulatory mechanisms
Mehta, K., Patel, V., Busbridge, M., Renshaw, D., Zariwala, M., Evans, R. and Farnaud, S. 2013. Hepcidin transcription and peptide secretion are governed by different regulatory mechanisms. Fifth Congress of the International BioIron Society (IBIS), Biennial World Meeting. University College London 14 - 18 Apr 2013 Wiley. https://doi.org/10.1002/ajh.23453

Comparison Study of Oral Iron Preparations Using a Human Intestinal Model
Zariwala, M., Somavarapu, S., Farnaud, S. and Renshaw, D. 2013. Comparison Study of Oral Iron Preparations Using a Human Intestinal Model. Scientia Pharmaceutica. 81 (4), pp. 1123-1139. https://doi.org/10.3797/scipharm.1304-03

A novel approach to oral iron delivery using ferrous sulphate loadedsolid lipid nanoparticles
Zariwala, M., Elsaid, N., Jackson, T.L., Corral López, F., Farnaud, S., Somavarapu, S. and Renshaw, D. 2013. A novel approach to oral iron delivery using ferrous sulphate loadedsolid lipid nanoparticles. International Journal of Pharmaceutics. 456 (2), pp. 400-407. https://doi.org/10.1016/j.ijpharm.2013.08.070

Annexin-A1 protein and its relationship to cortisol
Fowkes, R.C., Moradi-Bidhendi, N., Branceleone, V., Zariwala, M., Brady, D., Jessop, D.S., Perretti, M. and Renshaw, D. 2013. Annexin-A1 protein and its relationship to cortisol. Psychoneuroendocrinology. 38 (5), pp. 722-727. https://doi.org/10.1016/j.psyneuen.2012.08.003

Attenuation of plasma annexin A1 in human obesity
Kosicka, A., Cunliffe, AD., MacKenzie, R., Zariwala, M., Perretti, M., Flower, R.J. and Renshaw, D. 2013. Attenuation of plasma annexin A1 in human obesity. FASEB Journal. 27 (1), pp. 1-11. https://doi.org/10.1096/fj.12-213728

Comparison study of iron preparations using a human intestinal model
Zariwala, M.G., Somavarapu, S., Farnaud, S. and Renshaw, D. 2013. Comparison study of iron preparations using a human intestinal model. Scientia Pharmaceutica. 81 (4), pp. 1123-1139. https://doi.org/10.3797/scipharm.1304-03

Interlinking diet, nutrition, menopause and recommended resources
Rajendram, R., Rajendram, R., Patel, V. and Preedy, V.R. 2013. Interlinking diet, nutrition, menopause and recommended resources. in: Hollins Martin, C.J., Watson, R.R. and Preedy, V.R. (ed.) Nutrition and diet in menopause Springer. pp. 451-456

Effect of Salvia miltiorrhiza on antioxidant enzymes in diabetic patients
Quan, Q., Quan, S. and Patel, V. 2013. Effect of Salvia miltiorrhiza on antioxidant enzymes in diabetic patients. in: Preedy, V.R. (ed.) Diabetes: oxidative stress and dietary antioxidants Academic Press. pp. 79-87

Hepcidin transcription and peptide secretion are governed by different regulatory mechanisms
Mehta, K., Patel, V., Busbridge Mark, Renshaw, D., Zariwala, M.G., Evans, R. and Farnaud, S. 2013. Hepcidin transcription and peptide secretion are governed by different regulatory mechanisms. American Journal of Hematology. 88, p. E55.

The role of cancer stem cells in osteosarcoma
Jenks, A., Smith, C.L., Patel, V. and Clements, M.O. 2013. The role of cancer stem cells in osteosarcoma. International society for stem cell research conference. Boston (Massachusetts, USA) June 12 – 15 2013

Damaging effect of free fatty acids and alcohol on hepatic mitochondrial function
Gyamfi, D., Clemens, D.L. and Patel, V. 2013. Damaging effect of free fatty acids and alcohol on hepatic mitochondrial function. Alcohol & Alcoholism. 48, pp. i48-i50.

Evaluation of behavioural and gastrointestinal symptoms in autistic children after visceral osteopathic treatment
Castellarin, I.B., Drysdale, I. and Patel, V. 2013. Evaluation of behavioural and gastrointestinal symptoms in autistic children after visceral osteopathic treatment. International Journal of Osteopathy. 16, pp. e13-e14.

Attenuation of plasma annexin A1 in human obesity
Kosicka, A., Cunliffe, A., Mackenzie, R.W.A., Gulrez Zariwala, M., Perretti, M., Flower, R.J. and Renshaw, D. 2013. Attenuation of plasma annexin A1 in human obesity. FASEB Journal. 27 (1), pp. 368-378. https://doi.org/10.1096/fj.12-213728

Hepatic mitochondrial dysfunction induced by fatty acids and ethanol
Gyamfi, D., Everitt, H.E., Tewfik, I., Clemens, D.L. and Patel, V. 2012. Hepatic mitochondrial dysfunction induced by fatty acids and ethanol. Free Radical Biology & Medicine. 53 (11), pp. 2131-2145. https://doi.org/10.1016/j.freeradbiomed.2012.09.024

Increased transferrin-bound iron uptake in HepG2 cells is followed by an increase in expression of the iron hormone hepcidin pre-and post-translationally
Mehta, K., Patel, V., Busbridge Mark, Renshaw, D., Zariwala, M., Evans, R. and Farnaud, S. 2012. Increased transferrin-bound iron uptake in HepG2 cells is followed by an increase in expression of the iron hormone hepcidin pre-and post-translationally. European Iron Club Annual Meeting 2012. Rennes, France 29 - 31 Aug 2012

Comparison of iron absorption from iron supplement preparations using an in vitro Caco-2 model
Zariwala, M., Farnaud, S. and Renshaw, D. 2012. Comparison of iron absorption from iron supplement preparations using an in vitro Caco-2 model. European Iron Club Annual Meeting 2012. Rennes, France 29 - 31 Aug 2012

DPPIV and macronutrients regulate the expression of PYY3–36 in human gut epithelial cells
Kosicka, A., Renshaw, D. and Zariwala, M. 2012. DPPIV and macronutrients regulate the expression of PYY3–36 in human gut epithelial cells. Society for Endocrinology BES 2012. Harrogate, UK Mar - Apr 2012 BioScientifica Ltd.. https://doi.org/10.1530/endoabs.31.P197

Ac 2-26, an annexin A1-derived peptide, reduces inflammation in human SGBS adipocytes after hypoxia treatment
Kosicka-Knox, A., Cunliffe, A., Mackenzie, R., Zariwala, M. and Renshaw, D. 2012. Ac 2-26, an annexin A1-derived peptide, reduces inflammation in human SGBS adipocytes after hypoxia treatment. 15th International & 14th European Congress of Endocrinology. Florence, Italy 05 - 09 May 2012 BioScientifica Ltd..

Annexin A1, an anti-inflammatory regulator, is expressed in human adipocytes
Kosicka-Knox, A., Cunliffe, A., Mackenzie, R., Zariwala, M. and Renshaw, D. 2012. Annexin A1, an anti-inflammatory regulator, is expressed in human adipocytes. Society for Endocrinology BES 2012. Harrogate, UK Mar - Apr 2012

Adipocyte pyruvate dehydrogenase kinase 4 expression is associated with augmented PPARγ upregulation in early-life programming of later obesity
Holness, M.J., Zariwala, M., Walker, C.G. and Sugden, M.C. 2012. Adipocyte pyruvate dehydrogenase kinase 4 expression is associated with augmented PPARγ upregulation in early-life programming of later obesity. FEBS Open Bio. 2, pp. 32-36. https://doi.org/10.1016/j.fob.2012.02.003

The central role of myostatin in skeletal muscle and whole body homeostasis
Elliott, B., Renshaw, D., Getting, S.J. and MacKenzie, R. 2012. The central role of myostatin in skeletal muscle and whole body homeostasis. Acta Physiologica. 205 (3), pp. 324-40. https://doi.org/10.1111/j.1748-1716.2012.02423.x

Chinese herbal products in the prevention and treatment of liver disease
Gyamfi, D., Everitt, H.E. and Patel, V. 2012. Chinese herbal products in the prevention and treatment of liver disease. in: Watson, R.R. and Preedy, V.R. (ed.) Bioactive food as dietary interventions for liver and gastrointestinal disease Academic Press. pp. 537-550

The central role of myostatin in skeletal muscle and whole body homeostasis
Elliott, B.T., Renshaw, D., Getting, S.J. and Mackenzie, R.W.A. 2012. The central role of myostatin in skeletal muscle and whole body homeostasis. Acta Physiologica. 205 (3), pp. 324-340. https://doi.org/10.1111/j.1748-1716.2012.02423.x

Dietary sugars: TLC screening of sugars in urine and blood samples
Alonso-Fernandez, J.R. and Patel, V. 2012. Dietary sugars: TLC screening of sugars in urine and blood samples. in: Preedy, V.R. (ed.) Dietary sugars: chemistry, analysis, function and effects Royal Society of Chemistry. pp. 186-205

Targeting the melanocortin receptor system for anti-stroke therapy
Holloway, P.M., Smith, H.K., Renshaw, D., Flower, R.J., Getting, S.J. and Gavins, F.N.E. 2011. Targeting the melanocortin receptor system for anti-stroke therapy. Trends in Pharmacological Sciences. 32 (2), pp. 90-98. https://doi.org/10.1016/j.tips.2010.11.010

Alterations to liver energy metabolism and cell death following alcohol exposure
Gyamfi, D., Clemens, D.L. and Patel, V. 2011. Alterations to liver energy metabolism and cell death following alcohol exposure. Alcohol & Alcoholism. 46, pp. p47-48.

Saliva: physiology and diagnostic potential in health and disease
Farnaud, S., Kosti, O., Getting, S.J. and Renshaw, D. 2010. Saliva: physiology and diagnostic potential in health and disease. ScientificWorldJournal. 10, pp. 434-456. https://doi.org/10.1100/tsw.2010.38

Changes in adipocyte circadian clock function via SRT1 and AMPK in programmed obesity
Caton, P.W., Zariwala, M., Holness, M.J. and Sugden, M.C. 2010. Changes in adipocyte circadian clock function via SRT1 and AMPK in programmed obesity. Diabetic Medicine. 27 (S1), pp. 1-36. https://doi.org/10.1111/j.1464-5491.2009.02935.x

Downstream gene activation of the receptor ALX by the agonist Annexin A1
Renshaw, D., Montero-Melendez, T., Dalli, J., Kamal, A., Brancaleone, V., D'Acquisto, F., Cirino, G. and Perretti, M. 2010. Downstream gene activation of the receptor ALX by the agonist Annexin A1. PLoS ONE. 5 (9) e12771. https://doi.org/10.1371/journal.pone.0012771

Apoptosis in alcoholic liver disease
Gyamfi, D., Everitt, H.E. and Patel, V. 2010. Apoptosis in alcoholic liver disease. in: Preedy, V.R. (ed.) Apoptosis: modern insights into disease from molecules to man Science Publishers. pp. 211-233

The effect of alcohol exposure on liver energy metabolism and cell death
Gyamfi, D., Clemens, D.L. and Patel, V. 2010. The effect of alcohol exposure on liver energy metabolism and cell death. Hepatology. 52, p. 455A.

Characterisation of cystathionine gamma-lyase/hydrogen sulphide pathway in ischaemia/reperfusion injury of the mouse kidney: an in vivo study
Tripatara, P., Patel, N.S.A., Brancaleone, V., Renshaw, D., Rocha, J., Sepodes, B., Mota-Filipe, H., Perretti, M. and Thiemermann, C. 2009. Characterisation of cystathionine gamma-lyase/hydrogen sulphide pathway in ischaemia/reperfusion injury of the mouse kidney: an in vivo study. European Journal of Pharmacology. 606 (1-3), pp. 205-209. https://doi.org/10.1016/j.ejphar.2009.01.041

S-Nitrosoglutathione inactivation of the mitochondrial and cytosolic BCAT proteins: S-Nitrosation and S-Thiolation
Coles, S.J., Easton, P., Sharrod, H., Hutson, S.M., Hancock, J., Patel, V. and Conway, M.E. 2009. S-Nitrosoglutathione inactivation of the mitochondrial and cytosolic BCAT proteins: S-Nitrosation and S-Thiolation. Biochemistry. 48 (3), pp. 645-656. https://doi.org/10.1021/bi801805h

PPARalpha deficiency impacts the regulation ofadipocyte leptin synthesis and secretion
Holness, M.J., Zariwala, M., Walker, C.G. and Sugden, M.C. 2009. PPARalpha deficiency impacts the regulation ofadipocyte leptin synthesis and secretion. Diabetic Medicine. 26 (S1), pp. 37-38. https://doi.org/10.1111/j.1464-5491.2009.02662.x

The molecular regulation of adipose-tissue gene expression by an early life intervention
Sugden, M.C., Zariwala, M., Nooristani, S. and Holness, M.J. 2009. The molecular regulation of adipose-tissue gene expression by an early life intervention. Diabetic Medicine. 26 (S1), pp. 37-38. https://doi.org/10.1111/j.1464-5491.2009.02662.x

PPARs and the orchestration of metabolic fuel selection
Sugden, M.C., Zariwala, M.G. and Holness, M.J. 2009. PPARs and the orchestration of metabolic fuel selection. Pharmacological Research. 60 (3), p. 141–150. https://doi.org/10.1016/j.phrs.2009.03.014

Liver metabolism: biochemical and molecular regulations
Gyamfi, D. and Patel, V. 2009. Liver metabolism: biochemical and molecular regulations. in: Preedy, V.R. (ed.) Nutrition, diet therapy, and the liver London CRC Press. pp. 3-15

Hepatic oxidative stress and apoptosis following acute alcohol
Everitt, H.E., Tewfik, I., Preedy, V.R. and Patel, V. 2009. Hepatic oxidative stress and apoptosis following acute alcohol. Alcohol & Alcoholism. 44, p. p85.

Melanocortin peptide therapy for the treatment of arthritic pathologies
Getting, S.J., Kaneva, M., Bhadresa, Y., Renshaw, D., Leoni, G., Patel, H.B., Kerrigan, M.J.P. and Locke, I.C. 2009. Melanocortin peptide therapy for the treatment of arthritic pathologies. The Scientific World Journal. 9, pp. 1394-1414. https://doi.org/10.1100/tsw.2009.163

Annexin 1 mediates the rapid anti-inflammatory effects of neutrophil-derived microparticles
Dalli, J., Norling, L.V., Renshaw, D., Cooper, D., Leung Kit-Y and Perretti, M. 2008. Annexin 1 mediates the rapid anti-inflammatory effects of neutrophil-derived microparticles. Blood. 112 (6), pp. 2512-2519. https://doi.org/10.1182/blood-2008-02-140533

Tomatoes: origin, cultivation techniques, and germplasm resources
da Silva, D.J.H., Abreu, F.B., Caliman, F.R.B., Antonio, A.C. and Patel, V. 2008. Tomatoes: origin, cultivation techniques, and germplasm resources. in: Preedy, V.R. and Watson, R.R. (ed.) Tomatoes and tomato products: nutritional, medicinal and therapeutic properties CRC Press. pp. 3-26

Effects of 4-hydroxynonenal on mitochondrial 3-hydroxy-3methylglutaryl (HMG-CoA) synthase
Patel, V., Spencer, C.H., Young, T.A., Lively, M.O. and Cunningham, C.C. 2007. Effects of 4-hydroxynonenal on mitochondrial 3-hydroxy-3methylglutaryl (HMG-CoA) synthase. Free Radical Biology and Medicine. 43 (11), pp. 1499-1507. https://doi.org/10.1016/j.freeradbiomed.2007.08.004

Therapeutic exploitation of endogenous anti-inflammatory mechanisms: old and new leads
Renshaw, D., Urquhart, P. and Perretti, M. 2007. Therapeutic exploitation of endogenous anti-inflammatory mechanisms: old and new leads. Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry. 5 (4), pp. 289-305. https://doi.org/10.2174/187152306778772838

Nutrition and alcoholic liver disease
Everitt, H.E., Patel, V. and Tewfik, I. 2007. Nutrition and alcoholic liver disease. Nutrition Bulletin. 32 (2), pp. 138-144. https://doi.org/10.1111/j.1467-3010.2007.00627.x

Prolactin in culture leads to a shift in stimulatory threshold but does not augment the K-ATP channel independent pathway for glucose-stimulated insulin secretion
Zariwala, M., Holness, M.J., Turner, M.D. and Sugden, M.C. 2007. Prolactin in culture leads to a shift in stimulatory threshold but does not augment the K-ATP channel independent pathway for glucose-stimulated insulin secretion. Diabetic Medicine. 24 (S1), p. 33. https://doi.org/10.1111/j.1464-5491.2007.02126.x

Enhancement of immune response of HBsAg loaded poly(L-lactic acid) microspheres against Hepatitis B through incorporation of alum and chitosan
Pandit, S., Cevher, E, Zariwala, M., Somavarapu, S. and Alpar, H.O. 2007. Enhancement of immune response of HBsAg loaded poly(L-lactic acid) microspheres against Hepatitis B through incorporation of alum and chitosan. Journal of Microencapsulation. 24 (6), p. 539–552. https://doi.org/10.1080/02652040701443700

Diet, obesity and diabetes: a current update
Walker, C.G., Zariwala, M.G., Holness, M.J. and Sugden, M.C. 2007. Diet, obesity and diabetes: a current update. Clinical Science. 112 (2), pp. 93-111. https://doi.org/10.1042/CS20060150

Adrenomedullin increases the expression of calcitonin-like receptor and receptor activity modifying protein 2 mRNA in human microvascular endothelial cells
Schwarz, N., Renshaw, D., Kapas, S. and Hinson, J.P. 2006. Adrenomedullin increases the expression of calcitonin-like receptor and receptor activity modifying protein 2 mRNA in human microvascular endothelial cells. Journal of Endocrinology. 190 (2), pp. 505-514. https://doi.org/10.1677/joe.1.06806

Intra-adrenal mechanisms in the response to chronic stress: investigation in a rat model of emotionality
Kosti, O., Raven, P.W., Renshaw, D. and Hinson, J.P. 2006. Intra-adrenal mechanisms in the response to chronic stress: investigation in a rat model of emotionality. Journal of Endocrinology. 189 (2), pp. 211-218. https://doi.org/10.1677/joe.1.06638

Early protein restriction attenuates effects of increased age to suppress the response of adipose-tissue LPL activity to feeding
Zariwala, M., Holness, M.J. and Sugden, M.C. 2006. Early protein restriction attenuates effects of increased age to suppress the response of adipose-tissue LPL activity to feeding. Diabetic Medicine. 23 (S2), pp. 31-138. https://doi.org/10.1111/j.1466-5468.2006.01875.x

Protein adduct species in muscle and liver of rats following acute ethanol administration
Patel, V., Worrall, S., Emery, P.W. and Preedy, V.R. 2005. Protein adduct species in muscle and liver of rats following acute ethanol administration. Alcohol & Alcoholism. 40 (6), pp. 485-493. https://doi.org/10.1093/alcalc/agh196

Liver dysfunction induced by bile duct ligation and galactosamine injection alters cardiac protein synthesis
Hunter, R.V., Patel, V., Baker, A.J. and Preedy, V.R. 2004. Liver dysfunction induced by bile duct ligation and galactosamine injection alters cardiac protein synthesis. Metabolism: Clinical and Experimental. 53 (8), pp. 964-968. https://doi.org/10.1016/j.metabol.2003.11.015

Protein metabolism in alcohol misuse and toxicity
Preedy, V.R., Koll, M., Adachi, J., Mantle, D., Patel, V. and Peters, T. 2003. Protein metabolism in alcohol misuse and toxicity. in: Watson, R.R. and Preedy, V.R. (ed.) Nutrition and alcohol: linking nutrient interactions and dietary intake London CRC Press. pp. 261-300

Chronic ethanol consumption increases the concentration of a 4-hydroxynonenal adduct with the mitochondrial hydroxy methyl glutaryl CoA synthase in liver
Patel, V., Spencer, C. and Cunningham, C.C. 2003. Chronic ethanol consumption increases the concentration of a 4-hydroxynonenal adduct with the mitochondrial hydroxy methyl glutaryl CoA synthase in liver. Hepatology. 38, p. p393.

Emerging techniques in biomedical research and their application to alcohol toxicity
Patel, V., Chaurand, P., Caprioli, R., Austen, B., Frears, E., Manca, F., Davies, H., Vrana, K., Wheeler, M. and Preedy, V.R. 2003. Emerging techniques in biomedical research and their application to alcohol toxicity. Alcoholism: Clinical and Experimental Research. 27 (2), pp. 348-353.

Bacterial lipopolysaccharide directly stimulates cortisol secretion in human adrenal cells
Vakharia, K., Renshaw, D. and Hinson, J.P. 2002. Bacterial lipopolysaccharide directly stimulates cortisol secretion in human adrenal cells. Endocrine Research. 28 (4), pp. 357-361. https://doi.org/10.1081/ERC-120016809

Bacterial Lipopolysaccharide directly stimulates cortisol secretion in human adrenal cells
Vakharia, K., Renshaw, D. and Hinson, J.P. 2002. Bacterial Lipopolysaccharide directly stimulates cortisol secretion in human adrenal cells. Endocrine Research. 28 (4), pp. 357-361. https://doi.org/10.1081/ERC-120016809

Altered hepatic mitochondrial ribosome structure following chronic ethanol consumption
Patel, V. and Cunningham, C.C. 2002. Altered hepatic mitochondrial ribosome structure following chronic ethanol consumption. Archives of Biochemistry and Biophysics. 398 (1), pp. 41-50. https://doi.org/10.1006/abbi.2001.2701

Chronic ethanol consumption increases the formation of an aldehyde-protein adduct in hepatic mitochondria
Patel, V., Young, T.A. and Cunningham, C.C. 2002. Chronic ethanol consumption increases the formation of an aldehyde-protein adduct in hepatic mitochondria. Alcoholism: Clinical and Experimental Research.

Regulation of rat adrenal vasoactive intestinal peptide content: effects of adrenocorticotropic hormone treatment and changes in dietary sodium intake
Hinson, J.P., Renshaw, D., Carroll, M. and Kapas, S. 2001. Regulation of rat adrenal vasoactive intestinal peptide content: effects of adrenocorticotropic hormone treatment and changes in dietary sodium intake. Journal of Neuroendocrinology. 13 (9), pp. 769-773. https://doi.org/10.1046/j.1365-2826.2001.00692.x

Cardioprotective effect of propranolol from alcohol-induced heart muscle damage as assessed by plasma cardiac troponin-T.
Patel, V., Ajmal, R., Sherwood, R., Sullivan, A., Richardson, P. and Preedy, V.R. 2001. Cardioprotective effect of propranolol from alcohol-induced heart muscle damage as assessed by plasma cardiac troponin-T. Alcoholism: Clinical and Experimental Research. 25 (6), pp. 882-889. https://doi.org/10.1111/j.1530-0277.2001.tb02294.x

Diarrhea reduces the rates of cardiac protein synthesis in myofibrillar protein fractions in rats in vivo
Hunter, R.V., Patel, V., Miell, J., Wong, H.J., Marway, J., Richardson, P. and Preedy, V.R. 2001. Diarrhea reduces the rates of cardiac protein synthesis in myofibrillar protein fractions in rats in vivo. Journal of Nutrition. 131 (5), pp. 1513-1519.

Acute doxorubicin (adriamycin) dosage does not reduce cardiac protein synthesis in vivo, but decreases diaminopeptidase I and proline endopeptidase activities
Zima, T., Tesar, V., Mantle, D., Koll, M., Patel, V., Richardson, P. and Preedy, V.R. 2001. Acute doxorubicin (adriamycin) dosage does not reduce cardiac protein synthesis in vivo, but decreases diaminopeptidase I and proline endopeptidase activities. Experimental and Molecular Pathology. 70 (2), pp. 154-161. https://doi.org/10.1006/exmp.2000.2353

Physiochemical properties of rat liver mitochondrial ribosomes
Patel, V., Cunningham, C.C. and Hantgan, R. 2001. Physiochemical properties of rat liver mitochondrial ribosomes. Journal of Biological Chemistry. 276 (9), pp. 6739-6746. https://doi.org/10.1074/jbc.M005781200

In vivo protein synthetic rates of atrial, ventricular, and pulmonary tissue proteins in aortic constriction, goldblatt, and bromoethylamine models of hypertension
Siddiq, T., Patel, V., Sherwood, R., Richardson, P. and Preedy, V.R. 2001. In vivo protein synthetic rates of atrial, ventricular, and pulmonary tissue proteins in aortic constriction, goldblatt, and bromoethylamine models of hypertension. Experimental and Molecular Pathology. 70 (1), pp. 19-30. https://doi.org/10.1006/exmp.2000.2333

Ethanol and oxidative stress
Sun, A., Ingelman-Sundberg, M., Neve, E., Matsumoto, H., Nishitani, Y., Minowa, Y., Fukui, Y., Bailey, S., Patel, V., Cunningham, C.C., Zima, T., Fialova, L., Mikulikova, L., Popov, P., Malbohan, I., Janebova, M., Nespor, K. and Sun, G. 2001. Ethanol and oxidative stress. Alcoholism: Clinical and Experimental Research. 25 (5 Suppl.), pp. 237S-243S.

Alpha-Tocopherol supplementation does not prevent acute alcohol-induced heart muscle damage
Koll, M., Patel, V., Sherwood, R.A., Seitz, H.K., Simanowski, U.A., Richardson, P.J., Peters, T.J. and Preedy, V.R. 2001. Alpha-Tocopherol supplementation does not prevent acute alcohol-induced heart muscle damage. Proceedings of the Nutrition Society. 60, p. P125A.

Ethanol and protein metabolism
Cunningham, C.C., Preedy, V.R., Paice, A., Hesketh, J., Peters, T., Patel, V., Volpi, E., Mawatari, K., Masaki, H., Mori, H. and Torii, K. 2001. Ethanol and protein metabolism. Alcoholism: Clinical and Experimental Research. 25 (5 Suppl.), pp. 262S-268S.

Chronic ethanol consumption alters the glutathione/glutathione peroxidase-1 system and protein oxidation status in rat liver
Bailey, S., Patel, V., Young, T.A., Asayama, K. and Cunningham, C.C. 2001. Chronic ethanol consumption alters the glutathione/glutathione peroxidase-1 system and protein oxidation status in rat liver. Alcoholism: Clinical and Experimental Research. 25 (5), pp. 726-733.

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