Apoptosis

, 14:1459 | Cite as

Diabetes and apoptosis: liver

Diabetes and Apoptosis

Abstract

The liver is a central regulator of glucose homeostasis and stores or releases glucose according to metabolic demands. In insulin resistant states or diabetes the dysregulation of hepatic glucose release contributes significantly to the pathophysiology of these conditions. Acute or chronic liver disease can aggravate insulin resistance and the physiological effects of insulin on hepatocytes are disturbed. Insulin resistance has also been recognized as an independent risk factor for the development of liver injury. In the healthy liver tissue homeostasis is achieved through cell turnover by apoptosis and dysregulation of the physiological process resulting in too much or too little cell death can have potentially devastating effects on liver tissue. The delineation of the signaling pathways that mediate apoptosis changed the paradigms of understanding of many liver diseases. These signaling events include cell surface based receptor-ligand systems and intracellular signaling pathways that are regulated through kinases on multiple levels. The dissection of these signaling pathways has shown that the regulators of apoptosis signaling events in hepatocytes can also modulate insulin signaling pathways and that mediators of insulin resistance in turn influence liver cell apoptosis. This review will summarize the potential crosstalk between apoptosis and insulin resistance signaling events and discuss the involved mediators.

Keywords

Insulin resistance Apoptosis Tumor necrosis factor Adipocytokines Serine kinases Liver disease 

Abbreviations

AMPK

5′AMP-activated protein kinase

CCl4

Carbon-tetrachloride

Erk

Extracellular-regulated kinase

FADD

Fas-associated death domain

gal

Galactosamine

GSK3

Glycogen synthase kinase 3

HCV

Hepatitis C virus

HCC

Hepatocellular carcinoma

HSC

Hepatic stellate cells

IKK

IκB kinase

iNOS

Inducible nitric-oxide synthase

LPS

Lipopolysaccharide

IL

Interleukin

IRS

Insulin receptor substrate

JAKs

Janus kinases

JNK

c-Jun N-terminal kinase

MAPK

Mitogen-activated protein kinases

mTOR

Mammalian target of rapamycin

NASH

Non-alcoholic steatohepatitis

NF-κB

Nuclear factor-κB

NKT

Natural killer T cells

PARP-1

Poly-(ADP-ribose) polymerase-1

PI3 K

Phosphoinositide 3-kinase

PPAR-α

Peroxisome proliferator-activated receptor-α

PKC

Protein kinase C

SOCS

Suppressors of cytokine signaling

SREBP

Sterol regulatory element-binding protein

STAT

Signal transducers and activators of transcription

TGFβ

Transforming growth factor β

TNF

Tumor necrosis factor α

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© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  1. 1.I. Medizinsiche KlinikUniversity Medical Center of the Johannes Gutenberg UniversityMainzGermany

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