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Role of ceramide in apoptosis and development of insulin resistance

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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.

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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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    D. I. Kuzmenko & T. K. Klimentyeva

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Original Russian Text © D. I. Kuzmenko, T. K. Klimentyeva, 2016, published in Biokhimiya, 2016, Vol. 81, No. 9, pp. 1155-1171.

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Kuzmenko, D.I., Klimentyeva, T.K. Role of ceramide in apoptosis and development of insulin resistance. Biochemistry Moscow 81, 913–927 (2016). https://doi.org/10.1134/S0006297916090017

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  • DOI: https://doi.org/10.1134/S0006297916090017

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