The Unfolded Protein Response: A Pathway That Links Insulin Demand with β-Cell Failure and Diabetes

Signal integration in the endoplasmic reticulum unfolded protein response

2007 • 5,948 citations

XBP1 mRNA Is Induced by ATF6 and Spliced by IRE1 in Response to ER Stress to Produce a Highly Active Transcription Factor

2001 • 3,799 citations

Global analysis of protein expression in yeast

2003 • 3,790 citations

Endoplasmic Reticulum Stress Links Obesity, Insulin Action, and Type 2 Diabetes

2004 • 3,671 citations

Protein translation and folding are coupled by an endoplasmic-reticulum-resident kinase

1999 • 3,119 citations

An Integrated Stress Response Regulates Amino Acid Metabolism and Resistance to Oxidative Stress

2003 • 3,079 citations

Regulated Translation Initiation Controls Stress-Induced Gene Expression in Mammalian Cells

2000 • 3,071 citations

Coupling of Stress in the ER to Activation of JNK Protein Kinases by Transmembrane Protein Kinase IRE1

2000 • 2,831 citations

IRE1 couples endoplasmic reticulum load to secretory capacity by processing the XBP-1 mRNA

2002 • 2,702 citations

Dynamic interaction of BiP and ER stress transducers in the unfolded-protein response

2000 • 2,696 citations

Mammalian thioredoxin is a direct inhibitor of apoptosis signal-regulating kinase (ASK) 1

1998 • 2,360 citations

Chemical Chaperones Reduce ER Stress and Restore Glucose Homeostasis in a Mouse Model of Type 2 Diabetes

2006 • 2,303 citations

Mediators of endoplasmic reticulum stress‐induced apoptosis

2006 • 2,212 citations

Endoplasmic reticulum stress: cell life and death decisions

2005 • 2,197 citations

XBP-1 Regulates a Subset of Endoplasmic Reticulum Resident Chaperone Genes in the Unfolded Protein Response

2003 • 1,979 citations

CHOP is implicated in programmed cell death in response to impaired function of the endoplasmic reticulum

1998 • 1,972 citations

Mammalian Transcription Factor ATF6 Is Synthesized as a Transmembrane Protein and Activated by Proteolysis in Response to Endoplasmic Reticulum Stress

1999 • 1,954 citations

CHOP induces death by promoting protein synthesis and oxidation in the stressed endoplasmic reticulum

2004 • 1,854 citations

Gadd153 Sensitizes Cells to Endoplasmic Reticulum Stress by Down-Regulating Bcl2 and Perturbing the Cellular Redox State

2001 • 1,840 citations

Reactive Oxygen Species Promote TNFα-Induced Death and Sustained JNK Activation by Inhibiting MAP Kinase Phosphatases

2005 • 1,727 citations

Reinitiation involving upstream ORFs regulates ATF4 mRNA translation in mammalian cells

2004 • 1,543 citations

Endoplasmic Reticulum Stress and Oxidative Stress: A Vicious Cycle or a Double-Edged Sword?

2007 • 1,455 citations

ER Stress Regulation of ATF6 Localization by Dissociation of BiP/GRP78 Binding and Unmasking of Golgi Localization Signals

2002 • 1,368 citations

ER Stress Triggers Apoptosis by Activating BH3-Only Protein Bim

2007 • 1,353 citations

Translational Control Is Required for the Unfolded Protein Response and In Vivo Glucose Homeostasis

2001 • 1,329 citations

ASK1 is essential for endoplasmic reticulum stress-induced neuronal cell death triggered by expanded polyglutamine repeats

2002 • 1,296 citations

IRE1 Signaling Affects Cell Fate During the Unfolded Protein Response

2007 • 1,292 citations

Feedback Inhibition of the Unfolded Protein Response by GADD34-Mediated Dephosphorylation of eIF2α

2001 • 1,283 citations

Decay of Endoplasmic Reticulum-Localized mRNAs During the Unfolded Protein Response

2006 • 1,231 citations

Diabetes Mellitus and Exocrine Pancreatic Dysfunction in Perk−/− Mice Reveals a Role for Translational Control in Secretory Cell Survival

2001 • 1,204 citations

Transcriptional induction of genes encoding endoplasmic reticulum resident proteins requires a transmembrane protein kinase

1993 • 1,197 citations

Low antioxidant enzyme gene expression in pancreatic islets compared with various other mouse tissues

1996 • 1,136 citations

IRE1-mediated unconventional mRNA splicing and S2P-mediated ATF6 cleavage merge to regulate XBP1 in signaling the unfolded protein response

2002 • 1,031 citations

Chronic Oxidative Stress as a Central Mechanism for Glucose Toxicity in Pancreatic Islet Beta Cells in Diabetes

2004 • 1,017 citations

Oxidative protein folding in eukaryotes

2004 • 990 citations

Transcriptional Induction of Mammalian ER Quality Control Proteins Is Mediated by Single or Combined Action of ATF6α and XBP1

2007 • 976 citations

TRB3, a novel ER stress-inducible gene, is induced via ATF4–CHOP pathway and is involved in cell death

2005 • 933 citations

BI-DIRECTIONAL PROTEIN TRANSPORT BETWEEN THE ER AND GOLGI

2004 • 880 citations

Targeted disruption of the Chop gene delays endoplasmic reticulum stress–mediated diabetes

2002 • 858 citations

EIF2AK3, encoding translation initiation factor 2-α kinase 3, is mutated in patients with Wolcott-Rallison syndrome

2000 • 800 citations

Endoplasmic reticulum stress contributes to beta cell apoptosis in type 2 diabetes

2007 • 799 citations

Endoplasmic Reticulum Stress Activates Cleavage of CREBH to Induce a Systemic Inflammatory Response

2006 • 788 citations

CHOP Is Involved in Endoplasmic Reticulum Stress-induced Apoptosis by Enhancing DR5 Expression in Human Carcinoma Cells

2004 • 769 citations

Adaptation to ER Stress Is Mediated by Differential Stabilities of Pro-Survival and Pro-Apoptotic mRNAs and Proteins

2006 • 767 citations

FOXO transcription factor activation by oxidative stress mediated by the small GTPase Ral and JNK

2004 • 752 citations

Targeted disruption of the Chop gene delays endoplasmic reticulum stress–mediated diabetes

2002 • 724 citations

Beneficial effects of antioxidants in diabetes: possible protection of pancreatic beta-cells against glucose toxicity.

1999 • 716 citations

Autocrine Tumor Necrosis Factor Alpha Links Endoplasmic Reticulum Stress to the Membrane Death Receptor Pathway through IRE1α-Mediated NF-κB Activation and Down-Regulation of TRAF2 Expression

2006 • 709 citations

Complementary Signaling Pathways Regulate the Unfolded Protein Response and Are Required for C. elegans Development

2001 • 693 citations

A Time-Dependent Phase Shift in the Mammalian Unfolded Protein Response

2003 • 670 citations

Two Distinct Stress Signaling Pathways Converge Upon the CHOP Promoter During the Mammalian Unfolded Protein Response

2002 • 666 citations

ATF6α Optimizes Long-Term Endoplasmic Reticulum Function to Protect Cells from Chronic Stress

2007 • 654 citations

Glutaredoxins: Glutathione-Dependent Redox Enzymes with Functions Far Beyond a Simple Thioredoxin Backup System

2004 • 643 citations

Nitric oxide-induced apoptosis in pancreatic β cells is mediated by the endoplasmic reticulum stress pathway

2001 • 594 citations

The unfolded protein response in nutrient sensing and differentiation

2002 • 592 citations

The PERK Eukaryotic Initiation Factor 2α Kinase Is Required for the Development of the Skeletal System, Postnatal Growth, and the Function and Viability of the Pancreas

2002 • 584 citations

On the mechanism of sensing unfolded protein in the endoplasmic reticulum

2005 • 561 citations

Free Fatty Acids and Cytokines Induce Pancreatic β-Cell Apoptosis by Different Mechanisms: Role of Nuclear Factor-κB and Endoplasmic Reticulum Stress

2004 • 560 citations

Endoplasmic reticulum stress induces calcium-dependent permeability transition, mitochondrial outer membrane permeabilization and apoptosis

2007 • 548 citations

Insulin gene mutations as a cause of permanent neonatal diabetes

2007 • 538 citations

Activation of Apoptosis Signal-Regulating Kinase 1 (ASK1) by Tumor Necrosis Factor Receptor-Associated Factor 2 Requires Prior Dissociation of the ASK1 Inhibitor Thioredoxin

2000 • 533 citations

METABOLIC COUPLING FACTORS IN PANCREATIC β-CELL SIGNAL TRANSDUCTION

1995 • 529 citations

Distinct roles of activating transcription factor 6 (ATF6) and double-stranded RNA-activated protein kinase-like endoplasmic reticulum kinase (PERK) in transcription during the mammalian unfolded protein response

2002 • 508 citations

Cytokines Downregulate the Sarcoendoplasmic Reticulum Pump Ca2+ ATPase 2b and Deplete Endoplasmic Reticulum Ca2+, Leading to Induction of Endoplasmic Reticulum Stress in Pancreatic β-Cells

2005 • 505 citations

An essential role in liver development for transcription factor XBP-1

2000 • 503 citations

Stress-induced gene expression requires programmed recovery from translational repression

2003 • 450 citations

Complexes containing activating transcription factor (ATF)/cAMP-responsive-element-binding protein (CREB) interact with the CCAAT/enhancer-binding protein (C/EBP)–ATF composite site to regulate Gadd153 expression during the stress response

1999 • 445 citations

XBP-1 is required for biogenesis of cellular secretory machinery of exocrine glands

2005 • 437 citations

Protein folding and quality control in the endoplasmic reticulum

2004 • 427 citations

Differential Contributions of ATF6 and XBP1 to the Activation of Endoplasmic Reticulum Stress-Responsive cis-Acting Elements ERSE, UPRE and ERSE-II

2004 • 421 citations

ER chaperone functions during normal and stress conditions

2004 • 414 citations

GLP-1 receptor activation improves β cell function and survival following induction of endoplasmic reticulum stress

2006 • 412 citations

Regulation of insulin biosynthesis in pancreatic beta cells by an endoplasmic reticulum-resident protein kinase IRE1

2006 • 412 citations

Ligand-independent Dimerization Activates the Stress Response Kinases IRE1 and PERK in the Lumen of the Endoplasmic Reticulum

2000 • 408 citations

Control of mRNA translation preserves endoplasmic reticulum function in beta cells and maintains glucose homeostasis

2005 • 408 citations

Ischemia-induced neuronal cell death is mediated by the endoplasmic reticulum stress pathway involving CHOP

2004 • 402 citations

High Expression Rates of Human Islet Amyloid Polypeptide Induce Endoplasmic Reticulum Stress–Mediated β-Cell Apoptosis, a Characteristic of Humans With Type 2 but Not Type 1 Diabetes

2007 • 392 citations

Protein‐misfolding diseases and chaperone‐based therapeutic approaches

2006 • 385 citations

Tumor Necrosis Factor α (TNFα) Induces the Unfolded Protein Response (UPR) in a Reactive Oxygen Species (ROS)-dependent Fashion, and the UPR Counteracts ROS Accumulation by TNFα

2005 • 370 citations

Structure of the Dual Enzyme Ire1 Reveals the Basis for Catalysis and Regulation in Nonconventional RNA Splicing

2008 • 362 citations

Derlin-2 and Derlin-3 are regulated by the mammalian unfolded protein response and are required for ER-associated degradation

2006 • 360 citations

Control of PERK eIF2α kinase activity by the endoplasmic reticulum stress-induced molecular chaperone P58 ^IPK

2002 • 360 citations

The crystal structure of human IRE1 luminal domain reveals a conserved dimerization interface required for activation of the unfolded protein response

2006 • 354 citations

Activation of apoptosis signal‐regulating kinase 1 by the stress‐induced activating phosphorylation of pre‐formed oligomer

2002 • 349 citations

Overexpression of GRP78 mitigates stress induction of glucose regulated proteins and blocks secretion of selective proteins in Chinese hamster ovary cells.

1992 • 348 citations

Two endoplasmic reticulum-associated degradation (ERAD) systems for the novel variant of the mutant dysferlin: ubiquitin/proteasome ERAD(I) and autophagy/lysosome ERAD(II)

2007 • 333 citations

Eukaryotic initiation factor eIF2

1999 • 328 citations

Translational control of proinsulin synthesis by glucose

1980 • 310 citations

Identification of novel stress-induced genes downstream of chop

1998 • 306 citations

The unfolded protein response sensor IRE1α is required at 2 distinct steps in B cell lymphopoiesis

2005 • 302 citations

Glucose stimulates proinsulin biosynthesis by a dose-dependent recruitment of pancreatic beta cells.

1988 • 300 citations

Translational Control and the Unfolded Protein Response

2007 • 299 citations

Signals for COPII-dependent export from the ER: what's the ticket out?

2003 • 290 citations

N-glycan structure dictates extension of protein folding or onset of disposal

2007 • 289 citations

CHOP/GADD153 is a mediator of apoptotic death in substantia nigra dopamine neurons in an in vivo neurotoxin model of parkinsonism

2005 • 281 citations

The unfolded protein response sensor IRE1α is required at 2 distinct steps in B cell lymphopoiesis

2005 • 280 citations

PERK EIF2AK3 control of pancreatic β cell differentiation and proliferation is required for postnatal glucose homeostasis

2006 • 270 citations

Diabetes Due to a Progressive Defect in β-Cell Mass in Rats Transgenic for Human Islet Amyloid Polypeptide (HIP Rat)

2004 • 260 citations

Disruption of the WFS1 gene in mice causes progressive -cell loss and impaired stimulus-secretion coupling in insulin secretion

2004 • 257 citations

Role of Disulfide Bridges Formed in the Luminal Domain of ATF6 in Sensing Endoplasmic Reticulum Stress

2006 • 254 citations

Redox Control of Exocytosis

2005 • 254 citations

Involvement of Oxidative Stress in the Pathogenesis of Diabetes

2007 • 244 citations

Wolfram (DIDMOAD) syndrome.

1997 • 242 citations

Cotranslocational Degradation Protects the Stressed Endoplasmic Reticulum from Protein Overload

2006 • 242 citations

Endoplasmic reticulum stress response is involved in nonsteroidal anti-inflammatory drug-induced apoptosis

2004 • 241 citations

WFS1-deficiency increases endoplasmic reticulum stress, impairs cell cycle progression and triggers the apoptotic pathway specifically in pancreatic β-cells

2006 • 237 citations

The function of GADD34 is a recovery from a shutoff of protein synthesis induced by ER stress—elucidation by GADD34‐deficient mice

2003 • 230 citations

Mice conditionally lacking the Wolfram gene in pancreatic islet beta cells exhibit diabetes as a result of enhanced endoplasmic reticulum stress and apoptosis

2005 • 222 citations

Oxidative Stress-mediated, Post-translational Loss of MafA Protein as a Contributing Mechanism to Loss of Insulin Gene Expression in Glucotoxic Beta Cells

2005 • 220 citations

Ubiquitinated-Protein Aggregates Form in Pancreatic β-Cells During Diabetes-Induced Oxidative Stress and Are Regulated by Autophagy

2007 • 218 citations

Chronic oxidative stress as a mechanism for glucose toxicity of the beta cell in Type 2 diabetes

2007 • 214 citations

Evolving questions and paradigm shifts in endoplasmic‐reticulum‐associated degradation (ERAD)

2003 • 214 citations

The Endoplasmic Reticulum Chaperone Improves Insulin Resistance in Type 2 Diabetes

2005 • 213 citations

Pancreatic β-Cell Failure and Diabetes in Mice With a Deletion Mutation of the Endoplasmic Reticulum Molecular Chaperone Gene P58IPK

2005 • 207 citations

The Role of p58^IPK in Protecting the Stressed Endoplasmic Reticulum

2007 • 203 citations

Oxidative Stress Induces Nucleo-Cytoplasmic Translocation of Pancreatic Transcription Factor PDX-1 Through Activation of c-Jun NH2-terminal Kinase

2003 • 202 citations

Intrinsic Capacities of Molecular Sensors of the Unfolded Protein Response to Sense Alternate Forms of Endoplasmic Reticulum Stress

2006 • 193 citations

Wolcott-Rallison Syndrome

2004 • 181 citations

WFS1/wolframin mutations, Wolfram syndrome, and associated diseases

2001 • 173 citations

Mutational spectrum of theWFS1 gene in Wolfram syndrome, nonsyndromic hearing impairment, diabetes mellitus, and psychiatric disease

2003 • 173 citations

BBF2H7, a Novel Transmembrane bZIP Transcription Factor, Is a New Type of Endoplasmic Reticulum Stress Transducer

2006 • 165 citations

Proinsulin maturation, misfolding, and proteotoxicity

2007 • 164 citations

The 58,000-Dalton Cellular Inhibitor of the Interferon-Induced Double-Stranded RNA-Activated Protein Kinase (PKR) Is a member of the Tetratricopeptide Repeat Family of Proteins

1994 • 162 citations

Metallothionein Protects Islets from Hypoxia and Extends Islet Graft Survival by Scavenging Most Kinds of Reactive Oxygen Species

2003 • 155 citations

Dominant-Negative Effects of a Novel Mutated Ins2 Allele Causes Early-Onset Diabetes and Severe β-Cell Loss in Munich Ins2C95S Mutant Mice

2007 • 150 citations

Acute nutrient regulation of the unfolded protein response and integrated stress response in cultured rat pancreatic islets

2007 • 148 citations

CHOP-Dependent Stress-Inducible Expression of a Novel Form of Carbonic Anhydrase VI

1999 • 146 citations

Islet Amyloid Polypeptide (IAPP) Transgenic Rodents as Models for Type 2 Diabetes

2006 • 142 citations

Infancy-onset diabetes mellitus and multiple epiphyseal dysplasia

1972 • 141 citations

Isofagomine- and 2,5-Anhydro-2,5-imino-<scp>d</scp>-glucitol-Based Glucocerebrosidase Pharmacological Chaperones for Gaucher Disease Intervention

2006 • 140 citations

The 58,000-dalton cellular inhibitor of the interferon-induced double-stranded RNA-activated protein kinase (PKR) is a member of the tetratricopeptide repeat family of proteins.

1994 • 136 citations

Induction of endoplasmic reticulum stress-induced β-cell apoptosis and accumulation of polyubiquitinated proteins by human islet amyloid polypeptide

2007 • 135 citations

Mitochondria and Endoplasmic Reticulum: The Lethal Interorganelle Cross-Talk

2005 • 132 citations

Global profiling of genes modified by endoplasmic reticulum stress in pancreatic beta cells reveals the early degradation of insulin mRNAs

2007 • 130 citations

Bax Inhibitor-1 Regulates Endoplasmic Reticulum Stress-associated Reactive Oxygen Species and Heme Oxygenase-1 Expression

2007 • 127 citations

Type 2 diabetes mellitus as a conformational disease.

2005 • 124 citations

Stressed-out B cells? Plasma-cell differentiation and the unfolded protein response

2003 • 121 citations

Divergent Roles of IRE1&amp;#945; and PERK in the Unfolded Protein Response

2006 • 120 citations

Gene Transfer of Manganese Superoxide Dismutase Extends Islet Graft Function in a Mouse Model of Autoimmune Diabetes

2003 • 118 citations

ERADicate ER Stress or Die Trying

2007 • 115 citations

Conservation and Diversity of the Cellular Disulfide Bond Formation Pathways

2006 • 113 citations

Glucose-induced Translational Control of Proinsulin Biosynthesis Is Proportional to Preproinsulin mRNA Levels in Islet β-Cells but Not Regulated via a Positive Feedback of Secreted Insulin

2003 • 112 citations

Overexpression of Glutathione Peroxidase With Two Isoforms of Superoxide Dismutase Protects Mouse Islets From Oxidative Injury and Improves Islet Graft Function

2005 • 107 citations

Insulin Mediates Glucose-stimulated Phosphorylation of PHAS-I by Pancreatic Beta Cells

1998 • 106 citations

Misfolded Proteins Traffic from the Endoplasmic Reticulum (ER) Due to ER Export Signals

2006 • 103 citations

Sodium-potassium ATPase 1 subunit is a molecular partner of Wolframin, an endoplasmic reticulum protein involved in ER stress

2007 • 101 citations

Endoplasmic Reticulum Stress-induced Death of Mouse Embryonic Fibroblasts Requires the Intrinsic Pathway of Apoptosis

2007 • 97 citations

Pancreatic Expression and Secretion of Human Islet Amyloid Polypeptide in a Transgenic Mouse

1994 • 89 citations

Cell Permeable Peptide of JNK Inhibitor Prevents Islet Apoptosis Immediately After Isolation and Improves Islet Graft Function

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Interferon-γ potentiates endoplasmic reticulum stress-induced death by reducing pancreatic beta cell defence mechanisms

2006 • 85 citations

Tumour necrosis factor receptor 1 mediates endoplasmic reticulum stress‐induced activation of the MAP kinase JNK

2006 • 82 citations

The Role of Nitric Oxide and the Unfolded Protein Response in Cytokine-Induced β-Cell Death

2007 • 82 citations

Glucose Activates a Protein Phosphatase-1-Mediated Signaling Pathway to Enhance Overall Translation in Pancreatic β-Cells

2006 • 80 citations

Association of Amino Acid Variants in the Activating Transcription Factor 6 Gene (ATF6) on 1q21-q23 With Type 2 Diabetes in Pima Indians

2006 • 78 citations

Exendin 4 controls insulin production in rat islet beta cells predominantly by potentiation of glucose-stimulated proinsulin biosynthesis at the translational level

2006 • 77 citations

Ethanol promotes endoplasmic reticulum stress‐induced neuronal death: Involvement of oxidative stress

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Measuring the balance between insulin synthesis and insulin release

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Wolcott-Rallison syndrome: Diabetes mellitus and spondyloepiphyseal dysplasia

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Autopsy Findings in the Wolcott-Rallison Syndrome

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A cis-Element in the 5′ Untranslated Region of the Preproinsulin mRNA (ppIGE) Is Required for Glucose Regulation of Proinsulin Translation

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Aberrant quality control in the endoplasmic reticulum impairs the biosynthesis of pulmonary surfactant in mice expressing mutant BiP

2007 • 61 citations

Vitamin C supplementation decreases insulin glycation and improves glucose homeostasis in obese hyperglycemic (ob/ob) mice

2002 • 58 citations

Probe-Independent and Direct Quantification of Insulin mRNA and Growth Hormone mRNA in Enriched Cell Preparations

2006 • 55 citations

Glucose-stimulated Protein Synthesis in Pancreatic β-Cells Parallels an Increase in the Availability of the Translational Ternary Complex (eIF2-GTP·Met-tRNAi) and the Dephosphorylation of eIF2α

2004 • 54 citations

Activating Transcription Factor 6 Polymorphisms and Haplotypes Are Associated with Impaired Glucose Homeostasis and Type 2 Diabetes in Dutch Caucasians

2007 • 54 citations

A kinase inhibitor activates the IRE1α RNase to confer cytoprotection against ER stress

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Accumulation of Misfolded Protein Aggregates Leads to the Formation of Russell Body-like Dilated Endoplasmic Reticulum in Yeast

1997 • 48 citations

Role of Endoplasmic Reticulum Calcium Disequilibria in the Mechanism of Homocysteine-Induced ER Stress

2007 • 44 citations

Catalysis of disulphide bond formation in the endoplasmic reticulum

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Reconstitution of glucotoxic HIT-T15 cells with somatostatin transcription factor-1 partially restores insulin promoter activity.

1998 • 41 citations

The Secretory Capacity of a Cell Depends on the Efficiency of Endoplasmic Reticulum-Associated Degradation

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Differential fate of glycoproteins carrying a monoglucosylated form of truncated N-glycan in a new CHO line, MadIA214, selected for a thermosensitive secretory defect

1997 • 29 citations

Endoplasmic Reticulum Stress and Inflammation in Obesity and Type 2 Diabetes

2007 • 26 citations

Polymorphisms in the Oxygen-Regulated Protein 150 Gene (ORP150) Are Associated With Insulin Resistance in Pima Indians

2002 • 21 citations

The EIF2AK3 gene region and type I diabetes in subjects from South India

2004 • 16 citations