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Biochemistry (Moscow)

, Volume 81, Issue 9, pp 913–927 | Cite as

Role of ceramide in apoptosis and development of insulin resistance

  • D. I. KuzmenkoEmail author
  • T. K. Klimentyeva
Review

Abstract

This review presents data on the functional biochemistry of ceramide, one of the key sphingolipids with properties of a secondary messenger. Molecular mechanisms of the involvement of ceramide in apoptosis in pancreatic β-cells and its role in the formation of insulin resistance in pathogenesis of type 2 diabetes are reviewed. One of the main predispositions for the development of insulin resistance and diabetes is obesity, which is associated with ectopic fat deposition and significant increase in intracellular concentrations of cytotoxic ceramides. A possible approach to the restoration of tissue sensitivity to insulin in type 2 diabetes based on selective reduction of the content of cytotoxic ceramides is discussed.

Keywords

ceramide sphingolipids apoptosis mediator insulin resistance diabetes 

Abbreviations

Apaf-1

apoptotic protease activating factor 1

Bcl-2

B-cell lymphoma 2 protein

CAPK

ceramide-activated protein kinase

CAPP

ceramide-activated protein phosphatase

c-Jun

c-Jun transcription factor

CRD

cysteine-rich domain

DAG

1,2-diacylglycerol

ER

endoplasmic reticulum

ERK-1/2

extracellular signal-regulated kinase 1/2

FA

fatty acid

FADD

Fas/Apo-1-associated with death domain

FAN

factor associated with neutral sphingomyelinase activation

Fas-L

Fas-ligand

FOXO1

forkhead box protein O1

GLUT4

glucose transporter 4

GSH

reduced glutathione

GSK3

glycogen synthase kinase 3

IFN-γ

interferon-γ

IL-1

interleukin-1

iNOS

inducible nitric oxide synthase

IRS-1

insulin receptor substrate 1

JNK

c-Jun N-terminal kinase

KSR

kinase suppressor of Ras

MAPK

mitogen-activated protein kinase

MLK3

mixed lineage kinase 3

mRNA

messenger RNA

NF-κB

nuclear factor kappa B

NO

nitric oxide

PDK1

3-phosphoinositide-dependent protein kinase 1

PDX-1

pancreatic and duodenal homeobox gene 1

PH-domain

pleckstrin homology domain

PI3K

phosphatidylinositol 3kinase

PKB/Akt

protein kinase B

PKC

protein kinase C

PP1

protein phosphatase 1

PP2A

protein phosphatase 2A

PtdIns(4,5)P2

phosphatidylinositol (4,5)-bisphosphate

PtdIns(3,4,5)P3

phosphatidylinositol (3,4,5)-trisphosphate

Rb

retinoblastoma protein

RNS

reactive nitrogen species

ROS

reactive oxygen species

SAPK

stress-activated protein kinase

SM

sphingomyelin

SMase

sphingomyelinase

S1P

sphingosin-1-phosphate

TNF-α

tumor necrosis factor-α

TNFR

tumor necrosis factor receptor

TRADD

TNF receptor-associated death domain protein

UPR

unfolded protein response

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© Pleiades Publishing, Ltd. 2016

Authors and Affiliations

  1. 1.Siberian State Medical UniversityMinistry of Healthcare of the Russian FederationTomskRussia

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