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Diabetes mellitus and apoptosis: inflammatory cells

  • Diabetes and Apoptosis
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Apoptosis Aims and scope Submit manuscript

Abstract

Since the early observation that similarities between thyroiditis and insulitis existed, the important role played by inflammation in the development of diabetes has been appreciated. More recently, experiments have shown that inflammation also plays a prominent role in the development of target organ damage arising as complications, with both elements of the innate and the adaptive immune system being involved, and that cytokines contributing to local tissue damage may arise from both infiltrating and resident cells. This review will discuss the experimental evidence that shows that inflammatory cell-mediated apoptosis contributes to target organ damage, from beta cell destruction to both micro- and macro-vascular disease complications, and also how alterations in leukocyte turnover affects immune function.

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Abbreviations

ACAT:

Acyl Co-A: cholesterol acyltransferase

AGE:

Advanced glycation end products

AIM:

Apoptosis inhibitor expressed by macrophages

APC:

Antigen presenting cells

APOε:

Apolipoprotein E

BMP:

Bone morphogenetic protein

CB2:

Canabinoid 2

CCL-2:

Chemokine ligand 2

CCR:

Chemokine receptor

CKD:

Chronic kidney disease

Cox-2:

Cyclooxygenase-2

CTGF:

Connective tissue growth factor

CTL:

Cytotoxic T lymphocyte

CVD:

Cardiovascular disease

DC:

Dendritic cells

DN:

Diabetic nephropathy

DR:

Diabetic retinopathy

EMT:

Epithelial-mesenchymal transformation

ER:

Endoplasmic reticulum

ESRD:

End-stage renal failure

FasL:

Fas ligand

FC:

Free cholesterol

FLIP:

FLICE-like inhibitory protein

FoxO:

Forkhead transcription factor

HGF:

Hepatocyte growth factor

IAP:

Inhibitor of apoptosis

IHG-1:

Induced in high glucose-1

IL:

Interleukin

IL-1Ra:

IL-1 receptor antagonist

iNOS:

Inducible NO synthase

IRAK:

Interleukin-1 receptor-associated kinase

LDL:

Low-density lipoprotein

LOX-1:

LDL receptor-1

Lp-PLA2:

Lipoprotein-associated phospholipase A2

LPS:

Lipopolysaccharide

M-CSF:

Macrophage colony-stimulating factor

MCP-1:

Monocyte chemotactic protein-1

MIF:

Migration inhibitory factor

NO:

Nitric oxide

NOD:

Nonobese diabetic

ox-LDL:

Oxidised low-density lipoprotein

PARP:

Poly (ADP-ribose) polymerase

PLC:

Phospholipase C

PPAR:

Peroxisome proliferator-activated receptor

RAAS:

Renin-angiotensin-aldosterone

RAGE:

Receptor for advanced glycation end products

RIP:

Rat insulin promoter

ROS:

Reactive oxygen species

SR-A:

Macrophage scavenger receptor A

STZ:

Streptozotocin

T1DM:

Type 1 diabetes mellitus

T2DM:

Type 2 diabetes mellitus

TCR:

T cell receptor

TIF:

Tubulointerstitial fibrosis

TIMP:

Tissue inhibitors of metalloproteinase

TLR:

Toll-like receptor

TNF:

Tumour necrosis factor

TRAIL:

TNF Related Apoptosis Inducing Ligand

Treg:

Regulatory T cells

UPR:

Unfolded protein response

UPS:

Ubiquitin-proteasome system

VCAM-1:

Vascular cell adhesion molecule-1

VLA-4:

Very late-acting antigen-4

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Acknowledgments

Work in the authors laboratory is funded by Science Foundation Ireland, The Health Research Board Ireland and the EU FP6 EICOSANOX Consortium (LSHM-CT-2004-005033). Aidan Ryan is the recipient of a Molecular Medicine Ireland Clinical Research Fellowship

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  1. UCD Diabetes Research Centre, UCD Conway Institute, School of Medicine and Medical Science, University College Dublin, Dublin, Ireland

    Aidan Ryan, Madeline Murphy, Catherine Godson & Fionnuala B. Hickey

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Correspondence to Catherine Godson.

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Ryan, A., Murphy, M., Godson, C. et al. Diabetes mellitus and apoptosis: inflammatory cells. Apoptosis 14, 1435–1450 (2009). https://doi.org/10.1007/s10495-009-0340-z

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