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Beta cell apoptosis in diabetes

  • Diabetes and Apoptosis
  • Published:
Apoptosis Aims and scope Submit manuscript

Abstract

Apoptosis of beta cells is a feature of both type 1 and type 2 diabetes as well as loss of islets after transplantation. In type 1 diabetes, beta cells are destroyed by immunological mechanisms. In type 2 diabetes abnormal levels of metabolic factors contribute to beta cell failure and subsequent apoptosis. Loss of beta cells after islet transplantation is due to many factors including the stress associated with islet isolation, primary graft non-function and allogeneic graft rejection. Irrespective of the exact mediators, highly conserved intracellular pathways of apoptosis are triggered. This review will outline the molecular mediators of beta cell apoptosis and the intracellular pathways activated.

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Abbreviations

T1DM:

Type 1 diabetes mellitus

CTL:

Cytotoxic T lymphocyte

β2m:

β2-microglobulin

NOD:

Non-obese diabetic

TNF:

Tumor necrosis factor

TNFR:

TNF receptor

FasL:

Fas Ligand

FADD:

Fas-associated death domain

BH3:

Bcl-homology domain 3

ALPS:

Autoimmune lymphoproliferation syndrome

lpr :

Lyphoproliferation

gld :

Generalized lymphoproliferative disease

IL-1:

Interleukin-1

IL-1R:

IL-1 receptor

IFN:

Interferon

IFNγR:

IFNγ receptor

IGRP:

Islet-specific glucose-6-phosphatase catalytic subunit-related protein

SOCS:

Suppressor of cytokine signaling

JNK:

c-Jun N-terminal kinase

NO:

Nitric oxide

iNOS:

Inducible NO synthase

XIAP:

X-linked inhibitor of apoptosis

ROS:

Reactive oxygen species

Gpx:

Glutathione peroxidase

SOD:

Superoxide dismutase

IBMIR:

Instant blood-mediated inflammatory reaction

IAPP:

Islet amyloid polypeptide

TXNIP:

Thioredoxin-interacting protein

T2DM:

Type 2 diabetes mellitus

CHOP:

C/EBP homologous protein

ER:

Endoplasmic reticulum

PERK:

PKR-like ER kinase

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Acknowledgments

We thank Dr. Janette Allison for critical reading of the manuscript. This work was supported by the National Health and Medical Research Council of Australia, the Juvenile Diabetes Research Foundation and the Australian Government through the Department of Health and Ageing.

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Correspondence to Helen E. Thomas.

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Thomas, H.E., McKenzie, M.D., Angstetra, E. et al. Beta cell apoptosis in diabetes. Apoptosis 14, 1389–1404 (2009). https://doi.org/10.1007/s10495-009-0339-5

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