Positions

Selected Publications

Academic Article

Year Title Altmetric
2018 Verapamil and beta cell function in adults with recent-onset type 1 diabetes.Nature Medicine.  24:1108-1112. 2018
2018 Diabetes pathogenic mechanisms and potential new therapies based upon a novel target called TXNIP.Current Opinion in Endocrinology and Diabetes.  25:75-80. 2018
2017 miR-204 Controls Glucagon-Like Peptide 1 Receptor Expression and Agonist Function.Diabetes.  67:256-264. 2017
2017 Encapsulation of Human Islets Using a Biomimetic Self-Assembled Nanomatrix Gel for Protection against Cellular Inflammatory ResponsesACS Biomaterials Science and Engineering.  3:2110-2119. 2017
2016 Keeping tabs on fructose.eLife.  5. 2016
2016 Islet ChREBP-β is increased in diabetes and controls ChREBP-α and glucose-induced gene expression via a negative feedback loop.Molecular Metabolism.  5:1208-1215. 2016
2016 miR-204 Targets PERK and Regulates UPR Signaling and β-Cell Apoptosis.Molecular Endocrinology -Baltimore-.  30:917-924. 2016
2016 TXNIP regulates myocardial fatty acid oxidation via miR-33a signaling.AJP - Heart and Circulatory Physiology.  311:H64-H75. 2016
2016 Calcium channel blocker use is associated with lower fasting serum glucose among adults with diabetes from the REGARDS study.Diabetes Research and Clinical Practice.  115:115-121. 2016
2016 Cytokines Regulate β-Cell Thioredoxin-interacting Protein (TXNIP) via Distinct Mechanisms and Pathways.Journal of Biological Chemistry.  291:8428-8439. 2016
2015 Altered myocardial metabolic adaptation to increased fatty acid availability in cardiomyocyte-specific CLOCK mutant mice.BBA - Biochimica et Biophysica Acta.  1861:1579-1595. 2015
2015 β-Cell MicroRNAs: Small but Powerful.Diabetes.  64:3631-3644. 2015
2014 MicroRNA-200 is induced by thioredoxin-interacting protein and regulates Zeb1 protein signaling and beta cell apoptosis.Journal of Biological Chemistry.  289:36275-36283. 2014
2014 Minireview: Thioredoxin-interacting protein: regulation and function in the pancreatic β-cell.Molecular Endocrinology -Baltimore-.  28:1211-1220. 2014
2014 Thioredoxin-interacting protein stimulates its own expression via a positive feedback loop.Molecular Endocrinology -Baltimore-.  28:674-680. 2014
2014 Thioredoxin-interacting protein promotes islet amyloid polypeptide expression through miR-124a and FoxA2.Journal of Biological Chemistry.  289:11807-11815. 2014
2014 Enhanced MIN-6 beta cell survival and function on a nitric oxide-releasing peptide amphiphile nanomatrix.International Journal of Nanomedicine.  9 Suppl 1:13-21. 2014
2013 Thioredoxin-interacting protein regulates insulin transcription through microRNA-204.Nature Medicine.  19:1141-1146. 2013
2013 FOXO1 competes with carbohydrate response element-binding protein (ChREBP) and inhibits thioredoxin-interacting protein (TXNIP) transcription in pancreatic beta cells.Journal of Biological Chemistry.  288:23194-23202. 2013
2012 Calcium channel blockers act through nuclear factor Y to control transcription of key cardiac genes.Molecular Pharmacology.  82:541-549. 2012
2012 Preventing β-cell loss and diabetes with calcium channel blockers.Diabetes.  61:848-856. 2012
2010 Intracellular shuttling and mitochondrial function of thioredoxin-interacting protein.Journal of Biological Chemistry.  285:3997-4005. 2010
2010 Lack of TXNIP protects against mitochondria-mediated apoptosis but not against fatty acid-induced ER stress-mediated beta-cell death.Diabetes.  59:440-447. 2010
2009 Glucose-stimulated expression of Txnip is mediated by carbohydrate response element-binding protein, p300, and histone H4 acetylation in pancreatic beta cells.Journal of Biological Chemistry.  284:16898-16905. 2009
2009 Diabetes induces and calcium channel blockers prevent cardiac expression of proapoptotic thioredoxin-interacting protein.AJP - Endocrinology and Metabolism.  296:E1133-E1139. 2009
2008 Lack of TXNIP protects beta-cells against glucotoxicity.Biochemical Society Transactions.  36:963-965. 2008
2008 Thioredoxin-interacting protein deficiency induces Akt/Bcl-xL signaling and pancreatic beta-cell mass and protects against diabetes.Federation proceedings.  22:3581-3594. 2008
2008 Thioredoxin-interacting protein: a critical link between glucose toxicity and beta-cell apoptosis.Diabetes.  57:938-944. 2008
2008 HIV-protease inhibitors induce expression of suppressor of cytokine signaling-1 in insulin-sensitive tissues and promote insulin resistance and type 2 diabetes mellitus.AJP - Endocrinology and Metabolism.  294:E558-E567. 2008
2007 Exenatide blocks JAK1-STAT1 in pancreatic beta cells.Metabolism.  56:915-918. 2007
2007 A cis-element in the 5' untranslated region of the preproinsulin mRNA (ppIGE) is required for glucose regulation of proinsulin translation.Cell Metabolism.  5:221-227. 2007
2006 Nitric oxide-dependent suppression of thioredoxin-interacting protein expression enhances thioredoxin activity.Arteriosclerosis, Thrombosis, and Vascular Biology.  26:2666-2672. 2006
2006 An analysis of high glucose and glucosamine-induced gene expression and oxidative stress in renal mesangial cells.Archives internationales de physiologie, de biochimie et de biophysique.  112:189-218. 2006
2006 Metabolism-independent sugar effects on gene transcription: the role of 3-O-methylglucose.Biochemistry.  45:11047-11051. 2006
2006 Exenatide inhibits beta-cell apoptosis by decreasing thioredoxin-interacting protein.Biochemical and Biophysical Research Communications.  346:1067-1074. 2006
2005 Gene expression profiling in INS-1 cells overexpressing thioredoxin-interacting protein.Biochemical and Biophysical Research Communications.  336:770-778. 2005
2005 Thioredoxin-interacting protein is stimulated by glucose through a carbohydrate response element and induces beta-cell apoptosis.Endocrinology.  146:2397-2405. 2005
2005 Increased insulin translation from an insulin splice-variant overexpressed in diabetes, obesity, and insulin resistance.Molecular Endocrinology -Baltimore-.  19:794-803. 2005
2004 Resistin serum levels in type 1 diabetes pre- and post-islet transplantation.Metabolism.  53:403-404. 2004
2004 Insulinomas and expression of an insulin splice variant.Lancet.  363:363-367. 2004
2003 Peak stimulated insulin secretion is associated with specific changes in gene expression profiles in sporadic insulinomas.Surgery.  134:982-987. 2003
2003 Resistin is expressed in pancreatic islets.Biochemical and Biophysical Research Communications.  310:641-645. 2003
2002 Oligonucleotide microarray analysis of intact human pancreatic islets: identification of glucose-responsive genes and a highly regulated TGFbeta signaling pathway.Endocrinology.  143:3695-3698. 2002
2002 A proinsulin gene splice variant with increased translation efficiency is expressed in human pancreatic islets.Endocrinology.  143:2541-2547. 2002
2001 Saccharomyces cerevisiae protein Pci8p and human protein eIF3e/Int-6 interact with the eIF3 core complex by binding to cognate eIF3b subunits.Journal of Biological Chemistry.  276:34948-34957. 2001
2001 Multiple roles for the C-terminal domain of eIF5 in translation initiation complex assembly and GTPase activation.EMBO Journal.  20:2326-2337. 2001
2001 A multifactor complex of eIF1, eIF2, eIF3, eIF5, and tRNA(i)Met promotes initiation complex assembly and couples GTP hydrolysis to AUG recognition.Cold Spring Harbor Symposia on Quantitative Biology.  66:403-415. 2001
2000 Discovery of a lipodystrophy gene: one answer, one hundred questions.European Journal of Endocrinology.  143:565-567. 2000
2000 A multifactor complex of eukaryotic initiation factors, eIF1, eIF2, eIF3, eIF5, and initiator tRNA(Met) is an important translation initiation intermediate in vivo.Genes and Development.  14:2534-2546. 2000
1999 Hope for insulin mimetic oral antidiabetic drugs.European Journal of Endocrinology.  141:561-562. 1999
1999 The crucial role of a phosphatase in insulin resistance and obesity.European Journal of Endocrinology.  141:323-324. 1999
1998 Insulin receptor substrate-2--a new candidate gene for NIDDM?European Journal of Endocrinology.  139:263-264. 1998
1998 [Chylothorax as the initial manifestation of malignant Hodgkin lymphoma].PRAXIS.  87:690-693. 1998
1998 Effects of glucagon-like peptide 1 (7-36 amide) on glucose kinetics during somatostatin-induced suppression of insulin secretion in healthy men.Hormone Research.  49:221-225. 1998
1997 The role of glucagon-like peptide 1 in the regulation of glucose homeostasis and satiety.European Journal of Endocrinology.  137:220-221. 1997
1997 Absence of short-term effects of glucagon-like peptide-1 and of hyperglycemia on plasma leptin levels in man.Metabolism.  46:723-725. 1997
1997 Short-term effects of glucagon-like peptide 1 (7-36 amide) on leucine kinetics in healthy volunteers.Clinical Nutrition.  16:101-102. 1997
1997 Effects of glucagon-like peptide 1 (7-36 amide) on whole-body protein metabolism in healthy man.European Journal of Clinical Investigation.  27:10-16. 1997
1996 Insulin-independent effects of glucagon-like peptide 1 (7-36 amide) (glp-1) on glucose kinetics in manFederation proceedings.  10. 1996
1996 The peroxisome proliferator-activated receptor alpha is a phosphoprotein: regulation by insulin.Endocrinology.  137:4499-4502. 1996
1996 Peroxisome proliferator-activated receptors: a nuclear hormone receptor involved in adipocyte differentiation and lipid homeostasis.European Journal of Endocrinology.  134:541-542. 1996

Research Overview

  • Molecular biology of diabetes, beta cell biology, apoptosis, oxidative stress, transcriptional regulation of gene expression, diabetes complications

    Research Description:
    Diabetes is a rapidly growing public health issue characterized by elevated blood glucose levels and high morbidity and mortality. Under normal conditions, insulin, a hormone produced exclusively in the pancreatic beta cells, maintains blood glucose levels within the normal range. Loss of these pancreatic beta cells by programmed cell death (apoptosis) is a key feature of diabetes. Therefore, finding a target that could be used to block beta cell apoptosis and thereby preserve the patient’s own beta cell mass and insulin production would represent a major breakthrough for diabetes therapy. However, the mechanisms involved in beta cell death are not well understood. Dr. Shalev’s laboratory identified thioredoxin-interacting protein (TXNIP) (a protein involved in the cellular redox state) as such a potential target. When performing the first human pancreatic islet microarray study, Shalev found that TXNIP was the most dramatically up-regulated gene in response to glucose, suggesting that it might play an important role in beta cell biology. Subsequent analysis of the TXNIP promoter revealed that a unique carbohydrate response element was responsible for this glucose-induced TXNIP transcription. The Shalev group went on to show that TXNIP expression is increased in the islets of mice with diabetes and that TXNIP overexpression induces beta cell apoptosis. Moreover, the Shalev lab found that TXNIP plays a critical role in linking glucose toxicity to beta cell death and that TXNIP deficiency promotes beta cell survival. In fact, generalized or just beta cell-specific reduction of TXNIP expression was able to rescue mice from type 1 and type 2 diabetes proving that TXNIP represents an attractive therapeutic target. However, still very little is known about the processes controlling TXNIP and the Shalev lab is therefore now employing molecular biological in vitro approaches, as well as cell culture and various in vivo mouse models, to study the molecular mechanisms and signaling pathways involved in TXNIP regulation and function. Additional ongoing projects focus on the role of TXNIP in diabetic complications including diabetic cardiomyopathy and heart failure.
  • Principal Investigator On

  • UAB Diabetes Research Center - Enrichment Program  awarded by National Institute of Diabetes and Digestive and Kidney Diseases/NIH/DHHS 2018 - 2023
  • Development of An Early Diagnostic Biomarker and Novel Treatment Strategy for T1D  awarded by National Institute of Diabetes and Digestive and Kidney Diseases/NIH/DHHS 2018 - 2022
  • TXNIP Regulation of Endogenous Beta Cell Mass  awarded by National Institute of Diabetes and Digestive and Kidney Diseases/NIH/DHHS 2017 - 2022
  • Repurposing of Verapamil as a Beta Cell Survival Therapy in T1D  awarded by Juvenile Diabetes Research Foundation International 2014 - 2019
  • Targeting TXNIP to Enhance Beta Cell Mass in T1D  awarded by National Institute of Diabetes and Digestive and Kidney Diseases/NIH/DHHS 2014 - 2018
  • TXNIP Regulation of Endogenous Beta Cell Mass  awarded by National Institute of Diabetes and Digestive and Kidney Diseases/NIH/DHHS 2013 - 2017
  • Identification of a TXNIP-Regulated microRNA Involved in Insulin Production  awarded by American Diabetes Association, Inc. 2012 - 2015
  • Promote Beta-Cell Survival by Blocking TXNIP: Role of Calcium Channel Blocker  awarded by Juvenile Diabetes Research Foundation International 2010 - 2014
  • TXNIP Regulation of Endogenous Beta Cell Mass  awarded by National Institute of Diabetes and Digestive and Kidney Diseases/NIH/DHHS 2010 - 2013
  • Islet Cell Growth and Function: The Role of Thioredoxin-Interacting Protein  awarded by American Diabetes Association, Inc. 2010 - 2012
  • Education And Training

  • Doctor of Medicine, University of Basel
  • Full Name

  • Anath Shalev